We studied the effects of L-carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin-converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n=31), 2 g/day L-carnitine was added to therapy. L-Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3+/-7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2+/-8.7 years), 17 of the patients were men, and three were women. Twenty age-matched healthy subjects (mean age: 60.1+/-5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n=20), patients (n=51) had significantly higher red cell SOD activity (5633+/-1225 vs. 3202+/-373 U/g Hb, P<0.001). At the end of 1 month of L-carnitine therapy, red cell SOD activity showed an increase in group I (5918+/-1448 to 7218+/-1917 U/g Hb, P<0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190+/-545 to 5234+/-487 U/g Hb, P=0. 256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8-42.3%, P<0.001 in group I; 41. 5-43.8%, P<0.001 in group II). The improvement in LVEF was more significant in the L-carnitine group (4.5% vs. 2.3%, P<0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with L-carnitine treatment. L-Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.