Two adult men with severe hypogonadotrophic hypogonadism (persisting infantilism) were observed during long-term treatment with chorionic gonadotrophin (HCG) (23 and 6 months respectively) followed by treatment with human menopausal gonadotrophin (HMG) (for 7 and 12 months) and finally by combined treatment with HMG plus HCG (for 12 and 9 months). A study of hormone excretion, testicular biopsies and the clinical course showed that HMG given alone had little effect. Development of the testicular tubules was dependent upon the addition of HCG to the HMG, and the combined treatment induced a complete gonadal maturation. This LH action is presumably a direct effect on the tubules rather than indirect through Leydig cell stimulation. HMG acts synergistically with HCG in Leydig cell stimulation, and the results thus indicate a close interaction between FSH and LH on all testicular elements. No lasting effect of the long-term treatment was found. HMG has no antigenic properties in the human.