The hemodynamic and antiarrhythmic interactions between nadolol and a commonly used class I antiarrhythmic agent, quinidine or procainamide, were evaluated in 18 patients with ventricular arrhythmias in a double-blind, parallel study. Patients qualified for entry into the study if their ventricular arrhythmias remained poorly controlled (greater than or equal to 10 ventricular premature complexes/hr) with the class I agent alone and they had a left ventricular ejection fraction greater than 30%. Patients received their usual therapeutic doses of quinidine or procainamide throughout the study, which consisted of 3 treatment periods; a 2-week placebo treatment period, a 2-week open-label oral nadolol dose titration period, during which the dosages of nadolol were gradually increased from 40 mg daily to a maximum tolerated dose up to 120 mg daily, and a 4-week randomized, parallel comparison period during which patients were treated with either a class I agent alone or a combination of a class I agent and nadolol. Left ventricular ejection fractions by radionuclide ventriculography and 24-hour ambulatory electrocardiographic (Holter) recordings were obtained at the end of each treatment period. A positive treatment response was defined as greater than or equal to 75% reduction in ventricular premature complex frequency. During the dose titration phase, combination therapy with nadolol (mean dose 94 mg daily) and class I agents produced a mean decrease in ventricular premature complexes of 79% (p less than 0.01), and a mean decrease in ventricular couplets of 95% (p less than 0.01). A positive response was observed in 57% of patients treated with nadolol plus a class I agent.(ABSTRACT TRUNCATED AT 250 WORDS)