Pharmacological properties of ifenprodil, a vasodilating agent similar in chemical structure to isoxsuprine were investigated. In anesthetized dogs and cats, ifenprodil (0.3 approximately 1 mg/kg, i.v.) caused a temporary prominent depressor response with an increment in heart rate and an occasional enlargement of pulse pressure followed by a mildly durable hypotension. These two phases of hypotension of ifenprodil could not be demonstrated in spinal rats and cats. Ifenprodil also decreased the pressor response of norepinephrine and reversed the pressor effect of epinephrine to a depressor one. The lowering effect of ifenprodil on the constant-rate perfused pressure of vertebral artery in dogs was half as potent as isoxsuprine. Ifenprodil significantly reduced the contraction to norepinephrine in the isolated guinea-pig vas deferens. This was greater than the constrictor response produced by preganglionic sympathetic nerve stimulation. The inhibitory effect of ifenprodil was less potent than that of phentolamine on the responses to norepinephrine in isolated rabbit ascending aorta strips. In the isolated guinea-pig right atrium, ifenprodil (10(-5) g/ml) showed slightly negative inotropic and chronotropic effects, and reduced the responses to isoproterenol. It is suggested that the two phases of lowering effects of ifenprodil on the constant-rate perfusion pressure of either vertebral or femoral artery in dogs are due to a possible neurogenic and an alpha-adrenolytic action, but the precise mechanism is not clear. Ifenprodil like isoxsuprine has a weak beta-sympathetic effect.