The effect of acute (1500 IU/day for 3 days) and chronic HCG administration (1500 IU, 3 times weekly) on plasma testosterone levels in patients with Klinefelter's syndrome was compared with the response observed in patients with hypogonadotrophic eunuchoidism and in eugonadal male controls. Basal plasma testosterone levels in the Klinefelter patients were significantly lower than in the control subjects and significantly higher than in the patients with secondary hypogonadism. In all but one Klinefelter patient the plasma LH levels were markedly elevated even in the presence of normal testosterone levels. No significant correlation could be demonstrated between the plasma testosterone concentrations and the LH levels in the Klinefelter patients. Short term HCG administration resulted in a significant increase in the plasma testosterone levels in each of the 3 groups studied, independent of the basal value. The absolute increase in the Klinefelter patients was quantitatively comparable to that in the patients with secondary hypogonadism, but significantly lower than in the eugonadal controls. During long term HCG treatment the plasma testosterone levels definitely increased in both patient groups, but remarkably in the Klinefelter patients testosterone levels tended to decrease on continuing treatment, though in most patients testosterone levels remained higher than the pre-treatment values. The data on the effect of acute and chronic HCG administration on plasma testosterone levels in this study illustrate again that Leydig cells in Klinefelter's syndrome still retain a functional reserve, though less than in eugonadal males.