Cisapride, a prokinetic drug with a novel mechanism of action, was compared with another prokinetic drug, metoclopramide, and an H2-blocker, ranitidine, in the treatment of nonulcer dyspepsia. In a double-blind study, 60 patients with severe dyspeptic symptoms received cisapride 5 mg TID, metoclopramide 10 mg TID, or ranitidine 150 mg BID for 8 weeks. Symptoms were evaluated during treatment and 4 weeks after the end of therapy. All three drugs effectively controlled the symptoms of chronic functional upper gastrointestinal tract disorders. The prokinetic drugs, particularly cisapride, were significantly better than ranitidine in controlling symptoms, especially reflux symptoms. All three drugs were generally well tolerated; cisapride in particular was associated with fewer adverse effects.