This study was designed to compare the effect of oral administration of PGE2 (0.5 mg/kg) and ranitidine in larger (100 mg/dose) or smaller (10 mg/dose) doses on aspirin-induced gastric microbleeding and DNA loss determined chemically in gastric washings in eight healthy subjects. Aspirin (0.5 g) given four times daily greatly increased the rate of gastric bleeding and DNA loss and pretreatment with PGE2 or ranitidine in larger doses almost completely prevented these changes. Smaller non-antisecretory doses of ranitidine also reduced the rate of bleeding and DNA loss but to a lesser degree than PGE2. This study confirms that oral PGE2 has a protective action on gastric mucosa exposed to aspirin and that this property is also shared by ranitidine, a potent histamine H2-receptor antagonist.