The gastric antisecretory effects of three different doses of enisoprost, a new synthetic PGE1 analogue, were compared with placebo and misoprostol in 20 healthy male volunteers. Enisoprost 100, 200 and 400 micrograms all significantly (P less than 0.0001; ANOVA) suppressed histamine-stimulated acid and pepsin output when compared with placebo or misoprostol 200 micrograms. Misoprostol produced a significant decrease of stimulated acid output when compared with placebo (P = 0.0012). The concentration of pepsin in gastric juice was significantly (P less than 0.0001) decreased by enisoprost at the commencement of histamine stimulation. This effect was short-lived, and was maximal with enisoprost 400 micrograms. There was a significant dose-response relationship for enisoprost for inhibition of stimulated acid output (P = 0.0065). Enisoprost was well tolerated, and no consistent drug-related adverse effects were detected. The profile of antisecretory effect of enisoprost, producing marked suppression of both acid and pepsin secretion independently, is unusual. This combination of activity along with any mucosal protective properties might be particularly effective in the treatment of peptic ulcer disease.