The effects of exogenous and endogenous prostaglandin on rat pancreatic exocrine function were investigated in vivo and in vitro. Under stimulation by endogenous CCK or exogenous caerulein, protein output was significantly reduced by intravenous drip infusion of 16,16-dimethyl prostaglandin E2 (DMPGE2), and under stimulation by exogenous secretin, volume and bicarbonate output were markedly reduced by DMPGE2. Amylase release from isolated pancreatic acini was significantly reduced by DMPGE2 under stimulation by 10(-11)-3 x 10(-11) M CCK-8, and was not influenced by DMPGE2 under stimulation by secretin or by indomethacin under stimulation by caerulein. Basal amylase release was not influenced by DMPGE2 or indomethacin. Basal cellular cyclic AMP and cyclic GMP contents were not influenced by DMPGE2, and elevated cyclic GMP content under stimulation by caerulein was significantly reduced by DMPGE2. These findings suggest that pancreatic enzyme secretion is reduced by DMPGE2 under stimulation by physiological or pharmacological concentration of CCK, and one of which mechanism is direct effect of DMPGE2 on pancreatic acini, may be coupling with phosphatidylinositol breakdown system and without cyclic AMP.