Cardiovascular effects of therapeutic doses of tricyclic or tetracyclic antidepressants (TCA) were examined in 66 patients. After three weeks of therapy, heart rate and PR interval were increased (P less than .02, P less than .05), while prolongation of the QTc time and the QRS interval did not reach significant levels. We observed significant flattening of T waves (P less than .05), which was not associated with changes in the serum potassium level. These changes were reversible after treatment was discontinued. When therapy was maintained for 13 months, only the heart rate continued to be increased, whereas all other ECG values had returned to normal. The TCA therapy led to a significant prolongation of the preejection period (P less than .01) and slight shortening of the left ventricular ejection time, indicating a decrease in myocardial contractility. There was no difference of effects on the values studied between tricyclic and tetracyclic antidepressants.