The effect of early converting enzyme inhibition with enalapril on the extent of neurohumoral activation in acute myocardial infarction was evaluated in a randomized, placebo-controlled double blind fashion. Plasma levels of atrial natriuretic factor and noradrenaline on day 1, i.e. prior to randomization (n = 99), and on days 3 (n = 145) and 30 (n = 69) following myocardial infarction were determined. Enalapril did not significantly affect neurohumoral activation on day 3 (enalapril vs. placebo (mean (S.E.M.); atrial natriuretic factor: 35.3 (3.0) vs. 37.2 (2.9) pmol/l; noradrenaline: 2.82 (0.20) vs. 3.70 (1.02) nmol/l) or at 1 month (atrial natriuretic factor: 33.1 (3.0) vs. 32.4 (3.9) pmol/l; noradrenaline: 2.77 (0.25) vs. 2.82 (0.28) nmol/l). However, in myocardial infarction patients developing heart failure, a significant attenuation of the day 3 atrial natriuretic factor, but not of the noradrenaline response, was seen (atrial natriuretic factor: 47.0 (7.7) vs. 59.0 (6.4) pmol/l, P < 0.05; noradrenaline: 3.37 (0.42) vs. 6.59 (3.26) nmol/l, P = ns). In conclusion, enalapril did not significantly reduce neurohumoral activation in acute myocardial infarction, possibly because the activation in most patients is modest and confined to the early convalescent phase. However, in patients with myocardial infarction and heart failure enalapril therapy was associated with a reduction in early plasma atrial natriuretic factor levels, compatible with decreased cardiac filling pressures.