We analyzed the incidence of adverse reactions to antiarrhythmic drugs in 123 consecutive patients with a history of sustained ventricular tachycardia or ventricular fibrillation. Blood levels were measured serially and were maintained within the usual therapeutic range. Minor reactions were defined as those that required dosage reduction and major reactions as those that required drug discontinuation or permanent pacing for bradycardia. A total of 237 individual, oral drug trials were evaluated in the 123 patients. Adverse reactions were noted in 79 trials (33%) Fifty-nine (48%) of the 123 patients had one or more adverse reaction. Major reactions were noted in 36 patients (29%). Adverse effects occurred during 49% of trials with mexiletine hydrochloride, 44% of trials with amiodarone, 24% of trials with procainamide hydrochloride, and 18% of trials with quinidine sulfate or gluconate. In conclusion, clinically significant adverse reactions are common during drug therapy for ventricular arrhythmias. These observations indicate that with the drugs used in this study, an acceptable risk-benefit ratio will be possible only in patients at a significant risk for a symptomatic arrhythmia. Antiarrhythmic drug therapy in patients at low risk for serious arrhythmia should be discouraged.