Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2-4 weeks in a double-blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77% vs. 40%, P < 0.001) and 4 weeks (93% vs. 80%, P = 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer-related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow-up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole- and 37% of famotidine-treated patients (P > 0.1). The duration of ulcer-free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse.