This study was designed to determine whether exogenous hCG alone can complete spermiogenesis in men with isolated hypogonadotropic hypogonadism (IHH). hCG was administered to 22 men with IHH until maximal testicular growth was achieved. Their mean testicular volume increased from 5.5 +/- 1.1 (+/- SE) mL (pretreatment) to 10.8 +/- 1.6 mL (maximum) during treatment (P less than 10(-6)). The maximum mean testicular volume was highly positively correlated with initial volume (r = 0.84; P less than 10(-6)). All men attained normal serum testosterone levels, and 7 of 22 men achieved supraphysiological serum estradiol levels. During hCG treatment, 14 of the 22 men had sperm appear in their semen. Six of 11 men with complete gonadotropin deficiency, defined as an initial mean testicular volume less than 4 mL, became sperm positive during hCG treatment. In contrast, 9 of 11 men with partial gonadotropin deficiency (initial mean testicular volume of 4 mL or more) produced sperm during treatment (P less than 0.001). Sperm concentration was highly positively correlated with both pretreatment (r = 0.65; P less than 0.01) and final testicular volume (r = 0.73; P less than 0.0001). Of 13 men attempting to impregnate their partners, 7 were successful in initiating conception; a total of 8 pregnancies ensued. The sperm concentration at the time of conception was less than 10 million/mL in all but 1 man. Our study demonstrates that hCG, in the absence of exogenous FSH, can complete spermiogenesis in men with partial gonadotropin deficiency. The response to hCG in men with IHH is predicted by the initial testicular volume.