The effect of conventional high-osmolality contrast media (diatrizoate) and new low-osmolality contrast media (iopamidol) on plasma histamine, cyclic AMP and cyclic GMP levels have been examined in a group of 37 mongrel dogs. Plasma histamine levels have a tendency of elevation at five minutes after initiation of injection of diatrizoate and iopamidol in low dose (5 ml/kg). However, statistically no significant changes were found in either diatrizoate or iopamidol in low dose (5 ml/kg) or high dose (15 ml/kg). Plasma cyclic AMP levels have elevated significantly in twenty minutes after termination of injection of iopamidol in low dose (5 ml/kg) and in high dose (15 ml/kg). Also plasma cyclic AMP levels have elevated significantly in twenty minutes after termination of injection of diatrizoate in high dose (15 ml/kg). These findings indicate iopamidol has potential of elevating plasma cyclic AMP as compared with diatrizoate. Plasma cyclic GMP levels have elevated significantly in twenty minutes after termination of injection of diatrizoate in low dose (5 ml/kg) and in high dose (15 ml/kg). Also plasma cyclic GMP levels have elevated significantly in twenty minutes after termination of injection of iopamidol in high dose (15 ml/kg). These findings indicate diatrizoate has potential of elevating plasma cyclic GMP as compared with iopamidol. It is suggested that iopamidol has potential of elevation of plasma cyclic AMP that suppresses histamine release and diatrizoate has potential of elevation of plasma cyclic GMP that enhances histamine release. And so iopamidol is though to be minor histamine releaser than diatrizoate.