A compelling moral inquiry posing brilliantly as a procedural, John Patrick Shanley’s “Doubt” has shown itself to be as shrewdly conceived a play as Broadway has seen in years. But with three-quarters of the original cast giving way to a relatively starry new crew, the play has lost its balance a bit. This tilt is by no means crippling, but it is unfortunate. And the biggest casualty has been, well, doubt.

Mr. Shanley’s Tony- and Pulitzer-winning 2004 drama generated attention for its did-he-or-didn’t-he plot as well as its superb acting. (The exemplary Adriane Lenox is the lone holdover.) The story – about a nun’s investigation into possible sexual misconduct by a priest at her parish school circa 1964 – reveled in its ambiguity. Mr. Shanley and director Doug Hughes deftly used the upheavals of the Second Vatican Council as a backdrop for illustrating the dangers of certainty.

The play builds to a scorching confrontation between the dogmatic Sister Aloysius and the progressive, “accessible” Father Flynn. As performed by Cherry Jones and Brian O’Byrne, the scene whipped the audience’s sympathies between the two characters, as Sister Aloysius’s (very possibly correct) accusations were shown to stem both from her insights and from her blind spots. Both parties emerged questioning their cataclysmic choices, even those made with the best intentions, and the audience was left in a similar state.

But Ms. Jones and Mr. O’Byrne are gone, and in the hands of their replacements – stage veteran Eileen Atkins and Ron Eldard – the battle has become a mismatch. Ms. Atkins’s measured, insinuating interpretation towers over that of the more emphatic Mr. Eldard to the point where allegiances can’t help but shift toward the accuser. And when either of them wins this handily, everyone loses.

Ms. Atkins’s interpretation is more contemplative but no less expressive than that of Ms. Jones. Her Sister Aloysius is older and seemingly more fragile, yet she moves around the stage with the restlessness of an animal nearing its prey. But her voice stays remarkably level, even as her body language – particularly her piercing, unblinking eye contact – makes plain the effort behind maintaining this placidity. “If you forget yourself and study others, you will not be fooled,” Sister Aloysius counsels the younger Sister James (Jena Malone, the third new arrival), and Ms. Atkins shows both the wisdom and the folly behind such scrutiny.

This coiled, hypnotic take on Sister Aloysius rivals her predecessor’s extraordinary, albeit very different, performance. The same cannot be said for Mr. Eldard, a familiar film and television face with a legitimate number of stage credits. His weathered, broad-shouldered appearance, which earned him the Marlon Brando role in the ill-fated Broadway adaptation of “On the Waterfront,” would appear to be equally well suited for the scrappy, charismatic priest. But he puts Father Flynn’s turmoil on display far too broadly. Mr. Eldard fidgets, pauses, bellows, and broods. Each is a legitimate choice in and of itself, and Mr. Eldard has several fine moments, particularly during his two sermons. But the combined effect diminishes the role, pointing it in a very specific and not terribly rewarding direction.

Ms. Malone, for her part, grapples with Sister James’s Bronx accent and also with the basic tenets of physicality onstage – for example, what to do with her hands. She has been excellent in films, and perhaps a more contemporary, naturalistic stage role would mask her discomfort. As it stands now, though, she is simply not ready.

These misgivings aside, “Doubt” remains a beautifully paced, gorgeously assembled play, a piece of intelligent entertainment that comforts even as it challenges. And Messrs. Shanley and Hughes deserve credit for trying new shadings with a piece that did not need much “help.” As the austere Sister Aloysius puts it, “Satisfaction is a vice.” But change isn’t always a good thing. Sister Aloysius clearly believes this, and the cast assembled around her gifted new interpreter unwittingly demonstrates it.

Open run (219 W. 48th Street, between Broadway and Eighth Avenue, 212-239-6200).