Background: It has previously been shown that a combination of erythromycin and benzoyl peroxide is superior to either ingredient when used alone in the treatment of acne. A clindamycin/benzoyl peroxide combination gel might have an advantage over erythromycin/benzoyl peroxide gel because the former does not require refrigeration after it is dispensed. Objective: Our purpose was to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels. Methods: In two double-blind, randomized, parallel, vehicle-controlled trials, patients were treated for 11 weeks with once-nightly application of one of the above preparations. Evaluations were performed at 2, 5, 8, and 11 weeks and included lesion counts and assessment of global responses and irritant effects. Results: A total of 334 patients completed the study. All three active preparations were significantly superior to the vehicle in global improvement and in reducing inflammatory lesions and noninflammatory lesions. The combination gel was significantly superior to the two individual agents in global improvement and reduction of inflammatory lesions and also to the clindamycin gel in reducing noninflammatory lesions. There was no significant difference in tolerance to the active gels versus the vehicle gel. Conclusion: In the treatment of acne, topical clindamycin/benzoyl peroxide combination gel is well tolerated and superior to either individual ingredient. (J Am Acad Dermatol 1997;37:590-5.)