The actions of prostaglandins (PG) on cAMP in dispersed chief cells from guinea pig stomach were examined and compared to the actions of these agents on pepsinogen secretion. Maximal concentrations of A, B, or E prostaglandins caused a 2-5-fold increase in pepsinogen secretion and cellular CAMP. The relative order of potency for these actions was PGEs > PGAs > PGBs. Detection of prostaglandin-induced changes in cAMP was enhanced by adding a phosphodiesterase inhibitor to the incubation solution. The time courses for the effects of prostaglandins on pepsinogen secretion and CAMP were similar. With PGEl an increase in cAMP and pepsinogen secretion was detected by 1 min and was maximal by 7.5 min. Although significant increases in cAMP were detected with a ten-fold lower concentration of PGEs than PGAs, a maximal increase in cAMP was observed with t h e same concentration, 30 pM, of either agent. These data indicate that prostaglandins that stimulate pepsinogen secretion increase cAMP in dispersed chief cells. However, comparison of the dose-response curves for the actions of prostaglandins on pepsinogen secretion and cAMP revealed that detectable increases in cAMP occurred with concentrations of these agents that were about tenfold greater than those needed to stimulate pepsinogen secretion. Therefore, although the similarity in the kinetics and relative potencies of prostaglandininduced changes in cAMP and enzyme secretion provides further evidence that changes in cAMP play a role in t h e mediation of prostaglandin-induced pepsinogen secretion, the present data suggest the involvement of a cellular messenger in addition to CAMP.