Previous studies have shown that oral administration of minoxidil on 2 consecutive days produces an increase in heart rate and myocardial necrosis in Beagle dogs. Propranolol treatment (1.0 or 3.0 mg/kg every 8 h) did not abolish tachycardia and did not alter the incidence or severity of minoxidil-induced necrosis. In the present studies, pretreatment with either furosenmide (10 mg/kg) or hydrochlorothiazide (250 mg/kg) reduced serum potassium levels. However, only furosemide (for 11 days) reduced significantly the incidence of minoxidil-induced necrosis; only 2 of 10 animals (20%) developed myocardial lesions compared to 11 of 14 (79%) in the non-treated group. The incidence and severity of lesions in hearts from animals treated with furosemide for 3 days or hydrochlorothiazide for 11 days were essentially the same as in animals given minoxidil alone. Thus, furosemide, under certain conditions, can reduce the incidence of acute ventricular lesions induced by minoxidil.