This study investigates the interaction between histamine and the adenylate cyclase systems involved in the secretion of amylase from the guinea-pig pancreatic lobules. Histamine increased amylase release, reaching a maximum response at 10(-5) M. Similarly, vasoactive intestinal peptide (VIP) evoked significant increase in amylase release, though not in a dose-dependent fashion. When the pancreatic lobules were incubated with histamine in combination with VIP, forskolin or 3-isobutyl-1-methylxanthine (IBMX), amylase secretion was increased as compared to histamine alone. The stimulatory effect of VIP was also increased by the presence of forskolin or IBMX. These findings suggest that in guinea-pig pancreatic lobules, VIP, forskolin and IBMX, agents involved in the cyclic adenosine monophosphate (cAMP) pathway, potentiate histamine stimulated amylase release.