The cardiovascular effects of trazodone (TZD), amitriptyline (AMT) and placebo were studied in out-patients with major depression. AMT was shown to have the expected effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties. TZD, in contrast, had no quinidine-like effects and minor effects on systolic time intervals. However, it was not without any cardiovascular effects. Although TZD was shown to be a safer preparation than the reference drug AMT, long-term monitoring is needed to explain the minor effect on heart rate and T wave changes.