Sex hormone deficiency in schizophrenia has been suggested by the usual appearance of the psychosis in adolescence, the not infrequent somatic abnormalities, aberration of libido with often its eventual extinction, and, histologically, by the suggestive though not entirely accepted work of Mott (1919), Lewis (1923) and certain others implicating the testis. Accordingly, many workers have treated schizophrenia with sex hormone preparations empirically but without specific endocrine indications. The reported results have been inconsistent and disappointing. In this respect our experience with various hormones has been similar to that of others. The need for a physiological test to establish a diagnosis of endocrine deficiency and control appropriate therapy has been keenly felt. Values for the normal excretion of sex hormones at various stages during adolescence are not as yet established; estimations are not a practical possibility on a large scale, and with the exception of one excretion product of steroid metabolism with an androgenic action, namely, 17-keto-steroids, demand a biological technique. Testis biopsy, described by Charny (1940) and Lane Roberts (1939) is, therefore, a valuable diagnostic procedure, and possibly not without some therapeutic value. We have already described and classified a striking pathology of the testis in schizophrenia from studying biopsy material (Hemphill et al., 1940). The special features were atrophy of seminiferous epithelium, failure of spermatogenesis, thickening and hyalinization of the basement membrane and collapse or shrinkage of many tubules. We were unable to note consistent absence or marked reduction of interstitial elements in cases where secondary sexual characteristics were well developed, although the work of Mott (1919) drew particular attention to failure of internal secretion. The interpretation of the pathology is, of course, uncertain, but the atrophy of spermatogenetic structures suggested that there was a lack of normal or adequate gonadotrophic hormone necessary for the maintenance of spermatogenesis and the activity of the testis as a generative organ. For this reason we treated cases with gonadotrophic hormone of pregnant mare's serum (gestyl). This follicle-stimulating hormone is believed, in the male, to promote spermatogenesis. Treatment was dictated by the histology of the biopsy specimen. Gestyl was administered in 800 to 1,000 unit doses daily for variable periods of up to 48 days. Anti-hormones were tested for at the completion of treatment in the last series of cases, and further biopsies were made as a check-up for physiological efficacy.