We studied the effect of prostacyclin, PGI2, its chemical decomposition product, 6-oxo-PGF1 alpha, and a stable 5-6-dihydro analogue, 6-beta-PGI1, on gastric acid secretion, mucosal blood flow (14C-aminopyrine clearance), and mean arterial pressure in unanesthetized dogs. During submaximal acid secretion from a gastric fistula induced by intravenous histamine dihydrochloride (20 microgram kg-1 h-1), prostacyclin and its stable analogue, 6-beta-PGI1, reduced acid output with ID50s (dose causing 50% inhibition) of about 0.2 and 3.0 microgram kg-1 min-1 i.v., respectively, whereas 6-oxo-PGF1 alpha was inactive at 100 times the effective dose of prostacyclin. The ratio of mucosal blood flow to acid output remained unchanged during prostacyclin administration and was significantly elevated during 6-beta-PGI1 infusion, suggesting that with both compounds the changes in mucosal blood flow were not the cause of the antisecretory action. For doses causing equivalent antisecretory action, 6-beta-PGI1 lowered systemic arterial blood pressure much less than prostacyclin, indicating selectivity of action. Prostacyclin is unlikely to be a circulating antisecretory agent, but may play a role as a local humoral modulator of secretion and blood flow in the gastric mucosa.