In spontaneously hypertensive rats (SHR) between the ages of 6 and 8 weeks before the development of established hypertension, repeated daily subcutaneous administration of indomethacin, an inhibitor of cyclo-oxygenase, at a dose of 5 mg/kg/day enhanced significantly the development of spontaneous hypertension, but repeated daily subcutaneous administration of OKY 046, an inhibitor of thromboxane (TX)A2 synthetase, at a dose of 12 mg/kg/day did not alter the development of spontaneous hypertension. In SHR between the ages of 15 and 18 weeks with established hypertension, indomethacin or OKY 046 did not alter the high blood pressure as compared with the injection of vehicle. In both young and adult SHR, indomethacin decreased significantly urinary prostaglandin (PG)E2 and TXB2 excretion but not PGE2. These results indicate that cyclo-oxygenase products other than TXA2 may play a protecting role in the development of spontaneous hypertension in the rat whereas their contribution to the maintenance of hypertension may be unlikely. In addition, it is suggested that TXA2 may not be involved in the development and maintenance of spontaneous hypertension in the rat.