To investigate the control of relaxin (Rlx) secretion in men, we studied seminal plasma Rlx concentrations after physiologic and supraphysiologic gonadal stimulation. In the first experiment, 14 men with idiopathic hypogonadotropic hypogonadism provided semen samples at various time points before and during therapy with pulsatile GnRH. These data were compared to seminal plasma Rlx values in 5 normal men. In a second experiment, pharmacologic doses of hCG were administered in a fashion similar to that previously shown to have stimulated Rlx secretion from the CL of women. In men with idiopathic hypogonadotropic hypogonadism, no relationship was detected by linear regression analysis between seminal plasma Rlx and testosterone, testicular volume, ejaculate volume, or the appearance of sperm in the ejaculate. Rlx concentrations varied considerably between subjects (6-120 ng/ml) but remained fairly consistent within the same individual over time. Supraphysiologic gonadal stimulation with hCG similarly failed to alter seminal plasma Rlx (n = 5, mean +/- SEM; 48 +/- 9 ng/ml, 42 +/- 7 ng/ml, and 56 +/- 9 ng/ml on Days 1, 3, and 6, respectively; p < 0.05) in normal men despite dramatic increases in serum testosterone (763 +/- 25 ng/dl, 1702 +/- 136 ng/dl, and 1494 +/- 97 ng/dl on Days 1, 3, and 6, respectively; p < 0.05 vs. Day 1). Taken together, these data suggest that Rlx in men is secreted independently from direct gonadotropin control.