The pressor effect of 4-aminopyridine (4-AP) was studied in anesthetized cats and in isolated cat aortic ring preparations. A significant increase in blood pressure (38.9 +/- 11.4 mmHg) was observed following intravenous administration of 4-AP (0.3 mg/kg). The elevated blood pressure lasted for 1.3 h and returned to the control level after 1.5 h. The pressor effect of 4-AP was not blocked by prior administration of phentolamine (2 mg/kg i.v.) or by pretreatment with reserpine (2 mg/kg i.m., once a day for two consecutive days). In vitro, a dose-dependent tonic contraction of aortic ring was noted after addition of 4-AP into the bathing fluid. The ED50 of 4-AP was significantly greater than that of norepinephrine (NE) (8 X 10(-4) M vs. 10(-7) M). Phentolamine (10(-6) M) antagonized the contractile response to NE but not that to 4-AP, whereas verapamil (10(-5) M) attenuated the 4-AP induced contractile response. A diminished contractile effect was also obtained when aortic ring preparations were bathed in calcium-free solution. These data suggest that the sympathetic nervous system plays a minor role in the pressor effect of 4-AP and that the increased calcium influx may account, at least partially, for the vasoconstricting effect of 4-AP.