Urocortin-1 (Ucn-1), a member of the corticotropin-releasing factor family, has been shown in animal studies to have effects on the pituitary-adrenal axis, the cardiovascular system, circulating neurohormones, and renal function and to suppress appetite. For the first time in man we have evaluated these effects of infused Ucn-1 as well as actions on plasma ghrelin, a hormone known to increase appetite. We also assessed Ucn-1 pharmacokinetics. Eight healthy male volunteers consuming a diet of constant sodium and potassium content received 50 micro g Ucn-1 iv over 1 h in a placebo-controlled, randomized, time-matched, cross-over study. Ucn-1 infusion compared with placebo increased plasma levels of corticotropin [44.6 +/- 7.7 vs. 19.1 +/- 3.2 pg/ml (9.5 +/- 1.7 vs. 4.2 +/- 0.7 pmol/liter); P < 0.001], cortisol [15.6 +/- 1.6 vs. 7.7 +/- 1.4 micro g/dl (432 +/- 43 vs. 213 +/- 40 nmol/liter); P < 0.001], and atrial natriuretic peptide [26.2 +/- 3.4 vs. 21.3 +/- 2.2 pg/ml [8.5 +/- 1.1 vs. 6.9 +/- 0.7 pmol/liter); P = 0.019] while suppressing plasma ghrelin (P = 0.008). No hemodynamic or renal effects were observed at the dose used. The plasma Ucn-1 t(1/2) was 52 min based on a one-compartment model. In conclusion, a brief iv infusion of 50 micro g Ucn-1 stimulates plasma ACTH, cortisol, and atrial natriuretic peptide secretion and suppresses plasma ghrelin in healthy male volunteers. The latter effect might contribute to the anorexic action of Ucn-1.