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The effect of the depletion of germinal cells from the seminiferous tubules on serum follicle-stimulating (FSH) and luteinizing (LH) hormones was studied in young male rats. A single administration of 1-(N,N-diethylcarbamylmethyl)-2-4-dinitropyrrole (ORF 1616) seemed to damage primary spermatocytes and especially young spermatids. Whenever young spermatids (stages 1–8) were absent or at least decreased in number, a significant increase in serum FSH, and in some cases serum LH, was detected. The administration of another drug, bis(dichloroacetyl) diamine (WIN 18446) for 21 consecutive days induced a depletion of primary spermatocytes in the seminiferous tubules, which was followed by a depletion of spermatids, due to the lack of spermatocytes to generate them. By the time the seminiferous tubules showed partial or total disappearance of young spermatids, serum FSH and in some cases also serum LH levels were significantly raised. It is concluded that the germinal epithelium of rat testes exerts some kind of control on serum gonadotrophin levels. Young spermatids seem to be involved in this regulation.