TCV-116, an angiotensin II (AII) receptor antagonist, is a prodrug that is converted in vivo to the active form, CV-11974. CV-11974 selectively and competitively inhibited the specific binding of [125I]AII-(Sar1,lle8) to All subtype 1 (AT1) receptors in rabbit aortic membranes (Ki = 0.64 nM) and insurmountably inhibited the AII-induced maximal contractile response of rabbit aortic strips (pD'2 = 9.97). TCV-116 inhibited the AII-induced pressor response in rats (ID50 = 0.069 mg/kg. p.o.). In spontaneously hypertensive rats (SHR), TCV-116 had a sustained antihypertensive effect (ED25 = 0.68 mg/kg, p.o.). Repeated oral administration of TCV-116 (1 mg/kg) to SHR once daily for 2 weeks reduced blood pressure by 30-50 mmHg over 24 h. The antihypertensive effects of TCV-116 correlated well with the inhibition of AII-induced contractile responses of aortic strips prepared ex vivo after administration of TCV-116. TCV-116 had sustained effects in both 2 kidney, 1 clip hypertensive rats and in 1 kidney, 1 clip hypertensive rats, but had no effect in DOCA/salt hypertensive rats. Unlike enalapril, TCV-116 had no potentiating effect on the incidence of cough induced by citric acid in guinea pigs. These results suggest that TCV-116 is a promising antihypertensive agent with once daily administration.