It’s the most famous teenage kiss of all time. “O then, dear saint, let lips do what hands do. They pray,” Romeo declares on that fateful night of love at first sight at the Capulets’ masked ball. And so fraught a kiss for a young actor named Greg Shamie, just out of Circle in the Square theater school and hired for a modest, four-man version of the play staged in a storefront on the Lower East Side of Manhattan, that he wasn’t sure he was ready for it.

“I had never kissed a man before, and I was freaking out,” Shamie, who now has a wife and two young daughters, says of the events of 16 years ago. “I remember being cast and thinking, ‘Should I do this, or not?’ ”

(TERESA WOOD) - Students reading the roles of Romeo and Juliet together (Alex Mills, left, and Jefferson Farber) in “Shakespeare’s R&J,” now playing at Virginia’s Signature Theatre.

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He did, ultimately, do “this,” which turned into a show that would alter the course of Shamie’s and his fellow actors’ careers and cement the creative bona fides of its director-adapter, Joe Calarco. “Shakespeare’s R+J” the director called it, a piece that would move from the Expanded Arts company’s storefront on Ludlow Street to a year-long stay in a theater on West 42nd Street and eventually would be mounted to admiring reviews in such far-flung cities as London and Tokyo.

It was a trajectory Calarco could never have foreseen for a production that started in that makeshift downtown space with a smattering of audience members seated in a circle of folding chairs, watching as four young actors enact through the verse the story of their own sexual awakening. Nor could Calarco — whose directorial efforts have become a staple of, among other companies, Signature Theatre — have imagined that “Shakespeare’s R+J” would have such staying power that a full decade and a half after its debut, it would materialize yet again, on Signature’s main stage in the Village at Shirlington.

I first encountered “Shakespeare’s R+J” in its rawest shape, on Ludlow Street back in 1997, and ever since have felt a bond with its restless, nervy, fearless assault on a play so often performed it almost cannot avoid cliche. Calarco, it seems, has been unable to leave it alone, either. He’s revised the piece several times over the years; the published script is based on a 2003 London production. And, in fact, in this new, souped-up Signature version, embellished by the romantic flourishes in Chris Lee’s lighting and James Kronzer’s set design, the director has rewritten the ending: the piece now resounds more optimistically at the newfound sense of liberation expressed by its “Romeo,” played by Alex Mills.

“It’s been really great to do it again,” says Calarco, whose work at Signature has included well-received stagings of musicals such as “Urinetown” and “Assassins,” and a production of his modest original play, “Walter Cronkite is Dead.” “It’s made me remember that, wow, it actually worked. People would always say to me, ‘It’s the clearest “Romeo and Juliet” I’ve ever seen.’ ”

“Shakespeare’s R+J” takes place in a vague sort of modern day, in an unspecified learning institution with rigorous moral standards: The strong suggestion is offered, as the four young men march onto the stage in insignia-emblazoned jackets and begin to conjugate verbs in Latin, that this is a stifling religious school. After lights out, the boldest of the four pulls from a hiding place what seems a sacred book. It’s revealed to be “Romeo and Juliet” and, over the course of the next two hours, the students take turns reading from the work by flashlight and with youthful, roughhouse brio playing all of the characters.