BACKGROUND Endothelin, a natural peptide exhibiting potent vasoconstrictor activity, may play a crucial role in cardiovascular disease. The purpose of the present study was to compare the effect of an aerobic exercise bout on plasma ET levels in trained and untrained subjects. METHODS Nine healthy physically active males and nine sedentary controls cycled at 60% of their maximal aerobic power for 30 min. Plasma endothelin was determined by enzyme immunoassay at rest and 30 min after the end of the exercise. Endothelin values were compared through two-way (training status x time) analysis of variance with repeated measures on time. Changes in plasma volume, calculated from hematocrit and hemoglobin data, were compared through independent Student's t test. RESULTS We found a significant interaction of training status and time (p=0.05) resulting from opposite changes in the trained and untrained group (decrease in the former from 4.3+/-1.1 to 2.0+/-0.6 pg/ml vs. increase in the latter from 2.6+/-0.6 to 3.3+/-1.1 pg/ml). Changes in plasma volume with exercise were significantly different (decrease in the trained group vs. increase in the untrained group, p=0.03). CONCLUSIONS Our data indicate that aerobic training may reverse the augmentative effect of acute exercise on plasma endothelin levels. This adaptation may represent a novel beneficial effect of regular physical activity on human health.