The present study investigates the results of pretreatment with five prostaglandin (PG) synthetase inhibitors on effects of morphine on body temperature, pupillary diameter, body movement and production of exophthalmos in rat. Hyperthermia, induced by a low dose of morphine, was inhibited in animals pretreated with any of the PG synthetase inhibitors. However, PG synthetase inhibitors had no clear effect on hypothermia induced by higher doses of morphine. The duration of morphine-induced catalepsy was attenuated by pretreatment with the PG synthetase inhibitors in a dose-related manner. The exophthalmos induced by all doses of morphine was either shortened in duration or inhibited by sulindac, paracetamol or ibuprofen. Morphine-induced mydriasis was either attenuated or inhibited by paracetamol, ibuprofen or meclofenamic acid. The results suggest that endogenous PGs play a role in morphine-induced hyperthermia, catalepsy, exophthalmos and mydriasis whereas a physiological role for PGs in morphine-induced hypothermia was not indicated.