Two subjects affected by panhypopituitarism, 17 and 19 years of age, were evaluated. One of the patients was able to ejaculate sperm (14 X 10(6)/ml) after 12 months of hMG-hCG therapy (75 IU 2 degrees IRP HMG + 850 IU hCG twice a week). In the other subject sperm production was not achieved until 6 1/2 years of uninterrupted therapy had been completed although the hCG doses were doubled and then quadrupled. In the patient who responded promptly to the therapy, blood levels of both FSH (2.5) and LH (1.7 (mUI/ml 2 degrees IRP hMG-RIA methods) were indeed detectable through very low. In the patient resistant to the therapy, FSH levels were still detectable (2.2 mUI/ml), but LH was undetectable at all. The seminiferous tubules of this patient contained few spermatogonia, and these would be attributed to the action of FSH by itself. However, the importance of endogenous LH in determining the maturation of the testes is stressed by the very long period of hCG therapy required to obtain in this patient ejaculations of sperm. Careful evaluation must be made of circulating FSH and LH levels, of FSH and LH pituitary stores, and of testicular biopsy scores when assessing prognosis of fertility and adequate treatment of hypogonadotropic subjects. In cases of severe LH deficiency a delayed response of the testis would be expected and recovery of fertility considered possible even when gonadotropin therapy is unsuccessful for many years.