t has been called the most beautiful book in the world, and the most unreadable. Its hero has sex with buildings. It also has a nearly unpronouncable title, "The Hypnerotomachia Poliphili." The book was published in Venice in 1499, and there are perhaps 260 copies in existence, among them one in the rare book library at Princeton University.

"The Hypnerotomachia" is written in many languages, including Greek, Latin, Hebrew, Arabic, Chaldean, Italian, invented words and hieroglyphics, and it was not even fully translated until 1999, when the first complete English edition appeared. No one is quite sure what it is about, or even who wrote it.

But now Ian Caldwell and Dustin Thomason, both 28 and best friends since the third grade, have written "The Rule of Four," a novel in which they have invented a solution to both mysteries. And though it is filled with esoteric Renaissance scholarship and initially put off publishers, "The Rule of Four" (Dial Press) is flying off the shelves.

Since it was published on May 11, it has gone through 11 printings, and there are now 325,000 copies in circulation, leading book sellers to compare it to "The Da Vinci Code," by Dan Brown, which has been on The New York Times best-seller list for 60 weeks. "It's very unusual," said Sessalee Hensley, the fiction buyer for Barnes & Noble. "For a first novel, this is remarkably phenomenal." The novel will make a debut at No. 6 on The Times best-seller list on Sunday and will rise to No. 3 on the list on June 6.

Ms. Hensley said the sales of "The Rule of Four," "The Da Vinci Code" and "The Name of the Rose," by Umberto Eco, all of which have a historical background and involve complex clues to mysteries, show "the kind of market there is for books that have secret codes." Janet Maslin in her review of the book in The Times wrote, "The real treat here is the process of discovery, and those passages are written with precision and bravado."

In the real "Hypnerotomachia" this much is understood: a character, Poliphilo, dreams of his beloved Polia, and of his journeys in search of her. The title can be translated as "the struggle for love in a dream." Poliphilo has dreams within dreams, and when he has sex with buildings in at least one case his ecstasy is returned. The book is illustrated with exquisite woodcuts of the swooning hero and heroine, enchanted gardens, strange creatures, cherubs and nymphs.

The key to the true authorship of "The Hypnerotomachia" may lie hidden in the beautifully ornate letters at the beginning of each chapter, which spell out the words "Brother Francesco Colonna greatly loved Polia." There were two men with that name known at the time, one a Dominican monk in Venice, the other a Roman noble. There is also a theory that the book was written by the great Renaissance humanist and artist Leon Battista Alberti.

In "The Rule of Four" Tom, whose dead father was a Renaissance scholar obsessed with "The Hypnerotomachia," and Paul, who is writing his senior thesis on it, try to crack the book's mystery. The story is set against the background of Princeton's neo-Gothic eating clubs and underground passages. Tom and Paul are thwarted in their search by an evil professor, and there is a murder.

Mr. Caldwell and Mr. Thomason said they had written the book to preserve their friendship after graduating from college. "It was a wonderful opportunity for us to reconnect and force us to spend quality time together," Mr. Thomason said. "And to beat back reality and professional obligations."

The two grew up a few blocks apart in the Northern Virginia suburbs of Washington. They went to the same elementary and high schools, played on the same soccer team. Mr. Thomason's parents are analysts for Washington policy-research groups. Mr. Caldwell's father is a retired foreign service officer and his mother an educator for the Defense Department.

Mr. Caldwell went to Princeton and Mr. Thomason to Harvard. In 1998 they graduated from college and, suddenly the specter of adulthood loomed. They feared that their long friendship would inevitably wane. "We're big fans of the movie `Stand by Me,' " Mr. Caldwell said. "You know, where the narrator says, `I never had friends later on like the ones I had when I was 12."

This was not the first time they had written something together. There was their joint third-grade effort, "The Klutzy Kidnappers."

They began casting about for an idea. When Mr. Caldwell attended Princeton, he took Prof. Anthony Grafton's seminar on "Renaissance Art, Science and Magic" and wrote a paper on hieroglyphics in "The Hypnerotomachia."

Mr. Thomason remembered, "He said there was an acrostic coded into it which when you strung it together, the characters in it supposedly tell you who the author is. I thought: `This is a great way to start a book. What kind of secret could we invent, and what piece of Renaissance history could we connect it to to make a good yarn?' "

They decided to tie the mystery of the "Hypnerotomachia" to Savonarola, the fiery 15th-century Florentine monk who preached against the licentiousness of the Medici. In what is known as the "bonfire of the vanities," Savonarola held a public burning of the paintings, books, luxurious clothing and musical instruments that he saw as symbols of the city's excesses.

In the summer of 1998 the two authors began working in the basement of Mr. Caldwell's parents' house in Annandale, outlining the novel, and mapping out the solution to the mystery with mathematical precision.

Then Mr. Thomason went off to medical school at the Columbia University College of Physicians and Surgeons. Mr. Caldwell took a job as a software engineer. They sent e-mail drafts of the story back and forth and talked on the phone. Inevitably, they said, there were fights. "We would be yelling at each other over the phone," Mr. Thomason remembered. "But both fights and making up were natural to us. We've been fighting since we were kids."

By the end of the third year, Mr. Caldwell said, "We felt we could both write Tom's voice." Tom is the book's narrator.

Mr. Caldwell quit his job to write the book and moved in with his fiancÈe, Meredith Evans, a veterinarian. Mr. Thomason decided that in addition to his M.D. he would get an M.B.A. "to procrastinate, so we could publish the book," he said.

In 2001 they finished a draft and gave it to an agent who submitted it to various editors, all of whom turned it down. Susan Kamil, the editorial director of Dial Press, also rejected it, but she invited them to her office to talk about the manuscript and made suggestions. Their present agent, Jennifer Joel, was a classmate of Mr. Thomason's at Harvard.

They went back to the drawing board, incorporating Ms. Kamil's ideas. In 2002 they finished another draft. This time editors, including Ms. Kamil, wanted it. "We felt it was only poetic justice to choose Susan," Mr. Thomason said. They weren't finished, though. Ms. Kamil asked for more revisions. After 18 months of re-writes, the book was finally ready. They would not discuss the size of their advance.

The two friends are now hard at work on their second thriller. The subject is secret, though, like "The Rule of Four," it will combine past and present.

Now, Mr. Thomason said, "My parents are slowly getting over my not being a doctor."

"Yeah!" Mr. Caldwell said sarcastically, "He's a great failure!"