A double-blind multinational comparison of ranitidine 300 mg post evening meal (pem), ranitidine 300 mgnocte and cimetidine 800 mgnocte has been carried out in 1677 patients with endoscopically verified duodenal ulcer disease. Fifty-three percent of ulcers healed by two weeks during treatment with ranitidine 300 mg pem and 88% by four weeks, while the results for ranitidine 300 mgnocte were 50% and 86%, respectively, and 44% and 84% for cimetidine. The difference between ranitidine 300 mg pem and cimetidine was significant at two weeks (P=0.002, Mantel-Haenszel chi-squared test). The relative efficacy of the treatments was not dependent upon gender, smoking habit, alcohol intake, or ulcer frequency. However, the overall differences in healing between patients with small and large ulcers and patients with single and multiple ulcers were significantly different at weeks 2 and 4 (P<0.001). Significantly more patients treated with ranitidine (60%) had complete relief of epigastric pain than those treated with cimetidine (54%) (P<0.05). A meta-analysis of the four double-blind comparisons of ranitidine 300 mg pem (N=841) and 300 mgnocte (N=849), including the present study, failed to show the benefits of pem dosing, predicted from pharmacological studies.