Intravenous picrotoxin injection has been established as a model of producing arrhythmias, mainly through enhanced central sympathetic outflow. The effects of calcium-channel blockers, and a beta-blocker on these arrhythmias were tested in chloralose-anesthetized cats. Picrotoxin (10 mg/kg, i.v.) produced mostly ventricular, sometimes supraventricular tachycardias and ectopic beats, as well as a marked elevation of arterial blood pressure. Nifedipine at the doses of 2 micrograms/kg (i.v. or i.c.) and 5 micrograms/kg (i.v.) transiently suppressed the arrhythmias in some of the cats tested. With the dose of 10 micrograms/kg (i.v.), it promptly and consistently abolished the arrhythmias without recurrence and significantly reduced the blood pressure (-62 +/- 8/-59 +/- 8 mmHg, delta systolic pressure/delta diastolic pressure, p less than 0.001, n = 9). A similar degree of blood pressure reduction (-69 +/- 8/-67 +/- 7 mmHg, n = 6) after sodium nitroprusside (4-5 mg/kg, i.v.) injection abolished the arrhythmias in 4 of 6 cats; however, there was marked ECG evidence of myocardial ischemia in 3 cats. Verapamil (50 micrograms/kg, i.v.) transiently abolished the arrhythmias and significantly decreased the blood pressure (7/7 cats), whereas a larger dose (150 micrograms/kg) had a persistent effect (2/4 cats). Propranolol at a dose of 240 micrograms/kg also consistently abolished the arrhythmias without recurrence in all 4 cats. We conclude that nifedipine, verapamil and propranolol are effective in the treatment of picrotoxin-induced arrhythmias. This result indicates that calcium-channel blockers or beta-blockers may be clinically effective in the treatment or prevention of arrhythmias caused by intracranial lesions with enhanced sympathetic outflow.