10 healthy volunteers were randomized in two groups and treated with mianserin and amitriptyline for 6 days. Heart rate, arterial blood pressure, and blood levels of the drugs were measured daily. ECG and left-ventricular echocardiogram as a parameter of contractility were registered before as well as after 3 and 6 days of treatment with both drugs. The most striking result of our investigation was that amitriptyline-treated subjects showed a loss of myocardial contractility (-17% of the initial value) after 6 days of treatment; mianserin was ineffective in this respect. After both mianserin and amitriptyline an increase of the mean arterial blood pressure was observed; an increased heart rate was seen only in the amitriptyline group. No alterations in the parameters calculated from the ECG registrations were found in either group. The inability of mianserin to decrease cardiac contractility in the therapeutic dose range may favor this tetracyclic antidepressant over the tricyclic compound amitriptyline, especially in patients with cardiac disease.