The effects on pituitary-gonadal function of the potent gonadotropin-releasing hormone agonist D-trp6-pro9-n-ethylamide-LHRH (LRFA), 50 micrograms subcutaneously every 4th day for 10 weeks, were evaluated in seven normal men. A modest rise in mean serum LH levels was noted during the treatment period. Mean serum FSH levels were unchanged. Mean plasma testosterone (T) levels remained at 3.1 ng/ml or above. Sperm density during the control period varied widely within and between subjects, with a mean range of 69-137 million/ml. The mean sperm density fell to a nadir of 40 million/ml during treatment, but no consistent pattern was observed for each subject, with values varying between 4 and 368 million/ml. Elevated LH and T values were observed on eight and seven occasions, respectively, in five subjects, and corresponded to blood samples drawn 24 and 48 h after the last LRFA injection. Depressed T values were observed on 10 occasions in six patients, and in all but one, corresponded to blood drawn 72 and 96 h after the last injection. One subject had daily blood samples drawn at the start of and 4 weeks after beginning therapy. An agonist effect on LH, FSH, T, and estradiol was observed both times, although the effect was blunted on the second occasion. We conclude that treatment every 4 day with LRFA does not appear to be a promising regimen to induce consistent suppression of the pituitary-gonadal axis in man.