It has been reported that endothelin-1 (ET-1) increases in acute myocardial infarction (AMI). Experimental studies showed that captopril administration reduces ET-1 secretion. In addition, it was reported that the increased ET-1 levels are a negative prognostic index. The study sought to verify whether captopril can reduce plasma ET levels in the acute and subacute phases of reperfused anterior AMI. Forty-five patients, hospitalized for suspected anterior AMI within 4 h from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-2, were randomized (double blind) into two groups: group A (23; seven women/16 men) received captopril (as first dose) 2-4 h after starting thrombolysis (the dose was then increased up to 25 mg every 8 h). Group B (22; five women/17 men) received placebo after thrombolysis. All the patients met the reperfusion criteria. The two groups were similar with regard to age, sex, CK peak, ejection fraction, end-systolic volume and risk factors. Plasma ET levels were measured at entry, and 2, 12, 24, 48, and 72 h after starting thrombolysis. Mean concentrations of ET +/- SD: Group A basal, 1.50 +/- 0.67; at 2h, 2.31 +/- 1.24; 12 h, 1.84 +/- 1.45; 24 h, 1.30 +/- 0.72; 48 h, o.95 +/- 0.50; 72 h, 0.60 +/- 0.15 fmol/ml; p < 0.001. Group B basal, 1.58 +/- 0.83; at 2 h, 2.38 +/- 1.35; 12 h, 2.33 +/- 1.71; 24 h, 1.80 +/- 1.41; 48h, 1.46 +/- 0.88; 72 h, 0.93 +/- 0.44 fmol/ml; p < 0.001. Difference between the two groups was significant at the beginning of the test (between 2 and 12 h, p[=]0.002). After that, the values of the plasma endothelin decreased in parallel, p < 0.001. Our data suggest that captopril affects plasma ET levels in the acute and subacute phases of AMI. Moreover, these results provide additional evidence for a beneficial effect of early captopril treatment.