In the present study we investigated the role of epidermal growth factor (EGF) in cholecystokinin-octapeptide (CCK8)-induced inositol 1,4,5-trisphosphate (IP3) production and amylase release. The data show that high EGF concentrations (90 nM) increased the basal amylase release, but did not increase the acinar IP3 content. High EGF concentrations shifted the dose-response curve for CCK8-induced amylase release to lower CCK8 concentrations, whereas low EGF concentrations (17 nM) shifted this dose-response curve to higher CCK8 concentrations. 17 nM EGF inhibited CCK8-induced IP3 production during the whole period of observation of 5 min, whereas 90 nM EGF inhibited only the initial component (15 s) of CCK8-induced IP3 production. At later time points, 90 nM EGF increased CCK8-induced IP3 production. We conclude that low concentrations of EGF are inhibitory on CCK8-induced IP3 production and amylase release, whereas high EGF concentrations stimulate CCK8-induced amylase release.