Twenty-four-hour intragastric acidity was measured continuously over five separate occasions in 15 patients with healed duodenal ulcers. They were randomized to receive either placebo, cimetidine 800 mg, ranitidine 150 mg, famotidine 20 mg, or nizatidine 150 mg, given at 2200 hr in double-blind fashion. All H2-receptor blockers were more effective than placebo in suppressing both circadian (P less than 0.05-P less than 0.01) and nocturnal (P less than 0.002) gastric acidity, while there was no significant differences between the effects of the four active drugs in the same time periods. The percentage of nocturnal acid inhibition (2300-0800 hr) over placebo in terms of H+ values was virtually 100% with all active treatments. The effect on daytime (0800-1700 hr) and evening (1700-2300 hr) acidity of both placebo and the four H2-receptor antagonists was similar. Therefore, in the above doses H2-receptor blockers guarantee overnight anacidity to a similar degree and cause the physiological buffering of daily meals on gastric acidity to be fully exploited. Furthermore, the reducing effect of daily meals on drug action can be prevented. Since strong acid suppression strictly confined to the nocturnal period has been shown to be closely correlated with the highest ulcer healing rates, it is suggested that single low bedtime doses of H2-receptor antagonist should be evaluated in the acute treatment of duodenal ulcer.