The effects of cimetidine and gefarnate on endogenous prostacyclin, prostaglandin E2 and thromboxane were studied in vivo in rat gastric mucosa. The animals received cimetidine (20 mg/kg, i.p.) and/or gefarnate (100 mg/kg, s.c.) twice a day for 7 days. Gastric mucosal 6-keto-prostaglandin F1 alpha (as prostacyclin), prostaglandin E2 and thromboxane B2 (as thromboxane A2) were determined by radioimmunoassay. Cimetidine reduced prostacyclin, prostaglandin E2, but not thromboxane A2. Gefarnate inhibited the cimetidine-induced reduction of prostacyclin and prostaglandin E2; in cimetidine-untreated controls, it did not produce an increase in those prostaglandins and thromboxane A2 above the normal levels.