To assess its gonadotropin-inhibiting potency in man, three different doses of a GnRH antagonist [( Ac-D2-Nal1,D4-Cl-Phe2, D3-Pal3, Arg5,D4-p-methoxybenzoyl-2-amino butyric acid6,D-Ala10]GnRH; Nal-Glu GnRH antagonist) were given to six normal men. Single sc doses of 0.5, 1.5, and 5.0 mg Nal-Glu GnRH decreased mean serum immunoactive LH (iLH) to 45.0 +/- 5.7% (+/- SE), 37.0 +/- 4.9%, and 31.3 +/- 4.2% of baseline, respectively. Maximal suppression occurred between 4 and 8 h after drug injection. Serum bioassayable LH concentrations significantly diminished 8 h after injection of 1.5 and 5.0 mg GnRH antagonist, but not after the 0.5-mg dose. Mean serum testosterone (T) fell to 39.8 +/- 5.0%, 32.1 +/- 4.9%, and 20.7 +/- 4.4% of baseline, respectively, after the 0.5-, 1.5-, and 5.0-mg doses. The decreases in serum iLH and testosterone (T) were more sustained after the higher doses; serum iLH and T were significantly suppressed 24 h after administration of the 5.0-mg dose. Twenty-four-hour integrated serum iLH and T concentrations decreased in a dose-dependent manner. However, basal and 24-h integrated serum FSH concentrations were not significantly affected by the drug. No adverse systemic side-effects occurred. Thus, the Nal-Glu GnRH antagonist effectively decreases serum LH and T concentrations in a dose- and time-dependent manner, and it, therefore, has potential as a male contraceptive.