A study is presented evaluating the effect of selective germ cell depletion on regulation of plasma FSH concentrations in chronic vitamin A-deficient (VAD) male rats. Plasma FSH, LH and testosterone levels were measured to assess pituitary-testicular interaction and the specific activities of certain testicular enzymes were determined to evaluate seminiferous tubular function during genii cell reduction. By 130 days, the testicular effects of vitamin A deficiency were maximal and resulted in loss of all germinal elements beyond spermatogonia. However, Sertoli cells andLeydig cells appeared normal. Notably in the presence of an intact pituitary-testicular axis, as judged by a normal response to castration, plasma FSH levels in VAD rats were indistinguishable from age matched controls. Although plasma testosterone levels in VAD rats were significantly lower than normals, this was associated with a reduction in plasma LH as well. The physiologic significance of decreased androgen levels is not clear. At approximately 50 days, testis weight, seminiferous tubular diameter, and activities of lactic dehydrogenase (LDH), sorbitol dehydrogenase (SDH) and ³-glutamyl transpeptidase (GTP) were indistinguishable from normal. Thereafter, SDH and LDH levels fell markedly, concomitant with 80% reduction in testis weight and 40% in tubular diameter. LDH-X isozymes, determinedby polyacrylamide gel electrophoresis, were undetectable in testicular homogenates of VAD rats, whereas three distinct LDH-X bands were present in normal rats after the appearance of pachytene spermatocytes. In contrast to SDH and LDH, GTP levels actually increased above control values when germ cell loss was maximal. These data are compatible with the concept that the tubular anatomic site of feedback control for FSH is either the Sertoli cell and/or spermatogonia, and, although subtle changes in thepituitarytesticular axis cannot be entirely excluded, this is the first report of the maintenance of normal FSH levels in spite of a 90% loss of the germinal elements. The loss of activity of SDH and LDH and the rise in GTP levels during germ cell depletion support the use of certain enzymes as markers of spermatogenesis. The increase in GTP above control values is likely due to the relative enrichment of Sertoli cells during germ cell loss and supports the concept that GTP is a Sertoli cell marker. (Endocrinology95: 955, 1974)