The role of prostaglandins in peptic ulcer disease and their relation to Helicobacter pylori infection remain controversial. This study sought to compare the effects of oral nizatidine and ranitidine on the gastric mucosal release of prostanoids in duodenal ulcer (DU) patients and to correlate prostanoid concentrations with H. pylori status. Twenty-eight patients with DUs were randomized to receive either nizatidine or ranitidine. Nizatidine 300 mg at night elevated intraluminal PGE2 concentrations; 6-keto-PGF1 alpha concentrations also rose, but did not reach statistical significance. Ranitidine induced non-significant falls in PGE2 and 6-keto-PGE1 alpha concentrations. Patients with H. pylori infection had lower PGE2 and 6-keto-PGF1 alpha concentrations than non-infected patients, but nizatidine was equally effective in increasing prostanoid levels in both groups. These findings may be considered as favourable side effects of nizatidine with uncertain clinical significance. Further studies are needed to elucidate the synergism between prostanoids, eradication of H. pylori and nizatidine in the treatment of DU.