In order to study the hypophyseal-testicular axis in males with complete absence of germinal epithelium, the urinary total hypophyseal gonadotrophins (HG), urinary follicle stimulating hormone (FSH) and urinary luteinizing hormone (LH) were measured by specific bioassays in 12 males with classical Sertoli-cell-only syndrome and compared with HG, FSH and LH in normal and castrated men. HG and FSH were significantly higher than HG and FSH in normal men (P < 0.0025, P < 0.0005, respectively), but significantly lower than in castrated men (P < 0.001, P < 0.01, respectively). LH was not different from LH of normal men, but significantly lower than in castrated men (P < 0.0005). All patients had normal excretion of androgen metabolites (androsterone + aetiocholanolone) but a dexamethasone suppression test, performed in 8 subjects, revealed that in 2 cases of testicular origin, the values were below the normal range. The excretion of oestrogens was within the normal range. The presented data support the concept that the germinal epithelium produces a substance capable of inhibiting FSH secretion from the hypophyses, the Sertoli cell itself, however, having a basal production of this inhibitor. The finding of low excretion of testicular androgen metabolites in some of the patients and normal urinary LH, indicates that disturbances in the LH – testosterone feedback mechanism in such patients may occur and that the previous concept of isolated defects of spermatogenesis in all such patients was erroneous.