The relationship between the intactness of sustentacular (Sertoli) cell tight junctions and the status of spermatogenesis was examined in rats fed a vitamin-A-deficient diet after weaning (VAD rats). Both serum and testicular retinol concentrations of the VAD rats declined to a nadir by 80 days of age. At this time, it was observed that Sertoli cell tight junctions of the VAD animals were intact and complete spermatogenesis was maintained. Leakage in Sertoli cell tight junctions, as demonstrated by the presence of lanthanum in the adluminal compartment of the seminiferous epithelium, was first observed in 90-day-old VAD rats. Severe regression of spermatogenic cells was noted in 100-day or older VAD animals. These results suggest that severe germ cell loss observed during chronic vitamin A deficiency may result from abnormal intratubular environment due to the disruption of the blood-testis barrier.