Sixty-four patients with reproducible exercise-induced ventricular arrhythmias were enrolled in an open-label, multicenter study to assess the efficacy and safety of oral nadolol therapy. There were 53 men and 11 women ranging in age from 19 to 75 years (mean 53.9). The severity of arrhythmias varied from frequent ventricular premature beats to nonsustained and sustained ventricular tachycardias. Using serial treadmill exercise tests, patients underwent dose titration for 1 month and were followed up for 3 to 6 months. Depending on drug tolerance and response to treadmill exercise testing, the single daily required dose of oral nadolol ranged from 20 to 240 mg (average 66). Twenty-three (36%) of the patients experienced a total of 30 adverse effects of nadolol therapy; however, only 9 (14%) patients had to be withdrawn from the study. The adverse effects observed were those commonly associated with beta-adrenergic blocking agents, and all were dose-dependent and reversible. At the last patient visit, the severity of exercise-induced ventricular arrhythmias was significantly decreased compared with pretreatment in 36 (75%) of 48 evaluable patients. Eighteen (38%) of the patients demonstrated total suppression of arrhythmias. This was accompanied by significant increases from pretreatment in both the mean duration of symptom-limited exercise (+1.02 +/- 0.41 minutes, p less than 0.05) and the mean time of exercise required for arrhythmia induction (+1.80 +/- 0.66 minutes, p less than 0.01), a significant decrease from pretreatment in the mean peak exercise double-product (-4,775, p less than 0.001) and a decrease in the incidence of exercise-induced ST-segment depression (-33%).(ABSTRACT TRUNCATED AT 250 WORDS)