The effects of minoxidil on the electrocardiogram (EKG) were assessed in a prospective investigation of 112 patients with severe hypertension during an observation period representing 241.5 patient-years. Highly significant blood pressure reductions at rest and during exercise were achieved and maintained with the combination of minoxidil, beta-adrenergic blocking agents, and diuretics. In 90% of the patients, the initiation of minoxidil was associated with nonspecific T-wave changes in the EKG consisting of flattening or inversion, which ranged from slight to very marked. While these changes may initially appear disconcerting, the observations of this study show that they are not related to changes in heart rate or other clinical criteria associated with myocardial ischemia. The changes remain unaltered during the tachycardia of exercise, they are not influenced by beta-adrenergic blockade, and they generally revert to their control appearance during chronic treatment. During long-term treatment, a substantial reduction of the increased QRS voltages occurred.