The success of omeprazole in the healing of duodenal ulcer has been attributed to its profound and almost around-the-clock inhibition of acid, but the relevance of reducing meal-stimulated acid secretion exclusively has recently been emphasized in several clinical trials. For this reason, we used 24-h continuous intragastric pH monitoring to compare the pharmacodynamic effects of placebo, three fractioned premeal doses of cimetidine 400 mg and omeprazole 20 mg mane. Fifteen patients with duodenal ulcer in clinical remission were randomized to receive the above medications in single-blind fashion on three separate occasions, at least 2 wk apart. Both active regimens produced higher pH values (p < 0.05-0.001) than placebo, but omeprazole was much more effective than cimetidine (p < 0.01-0.001) during the various time intervals analyzed (24 h, evening, nighttime, daytime). The greater effectiveness of omeprazole was confirmed by its longer-lasting antisecretory action, insofar as the drug increased gastric pH above 3.0 units for about 21 h, whereas the daytime cimetidine regimen maintained this threshold for 7.30 h (p < 0.001) over the circadian cycle. As these markedly different pharmacodynamic effects have been proven to produce similar fast rates of duodenal ulcer healing in clinical trials, it is reasonable to assume that a small but well addressed reduction of gastric acidity can ensure the same therapeutic benefit as a strong and continuous acid inhibition. In this light, the acid peaks in response to meals seem to be important pathophysiological events, whose control is sufficient to permit quick ulcer healing.