In a randomized, placebo-controlled, double-blind clinical trial by Meyskens et al. the combination of difluoromethylornithine and sulindac has been shown to be strikingly effective for prevention of sporadic colorectal adenomas. This concomitant use of two drugs to suppress the progression of preneoplastic lesions represents the first major clinical success of the application of the principle of 'combination chemoprevention'. Neither drug alone has previously had clinical utility at the low doses used in this trial. The combination of the two agents has provided synergistic efficacy in suppression of carcinogenesis, while minimizing any undesirable adverse effects. This study should be the impetus for further clinical investigation of the use of multiple drugs for chemoprevention of cancer.