The antiarrhythmic effect of oral captopril was studied during the early (day 3) and late (day 14) phase of acute myocardial infarction among 304 patients in a randomized placebo-controlled substudy of ISIS-4. Ventricular arrhythmias (ventricular ectopic beats per hour) occurred significantly less frequently among captopril-allocated patients than among those allocated placebo at day 3 (logarithmic scale: 0.48 +/- 0.8 captopril vs 0.84 +/- 1.3 placebo; P < 0.003) and at day 14 (0.51 +/- 1.0 vs 0.77 +/- 1.3; P < 0.05). The number of patients with frequent ventricular arrhythmias (more than 10 ventricular ectopic beats per hour) was also significantly lower among those allocated captopril at day 3 (7.3% vs 14.4%; P < 0.05) and at day 14 (7.3% vs 14.8%; P < 0.05). These results support the hypothesis that the activation of the renin-angiotensin-aldosterone and sympathetic system may underlie heart rhythm disturbances in acute myocardial infarction, and that early use of converting enzyme inhibitor therapy may ameliorate these disturbances.