The responses of the mouse epididymal epithelium to subchronic doses of aflatoxin B1 were investigated in a histological study. Either few and large or small and profuse vacuoles containing an amorphous to dense periodic acid-Schiff-positive material were observed in the epithelium of all the segments of the epididymis. Resin-embedded semi-thin sections and transmission electron microscopy indicated that these vacuoles were intracellular. The cells that contained these vacuoles were quite different in organization and electron density from the cell types already established in the epididymal epithelium and are designated as pale vacuolated epithelial cells. Owing to aflatoxin B1 toxicity, the apical membrane of some of the principal cells, either individually or in groups, disintegrated so that the principal cells released their contents into the lumen of the duct through development of a 'fistula'. Spermatozoa from the ductal lumen entered the principal cell fistula and reached the basal lamina. If extravasation of the spermatozoa via this route occurred, it would bring about an autoimmune response, leading to the formation of spermatic granulomas and the generation of anti-sperm antibodies. Extravasation of spermatozoa seems to be offset by the underlying basal cell, which is presumed to develop into a pale vacuolated epithelial cell to enclose the disintegrating principal cells and the spermatozoa arriving at the principal cell. Thus, the development of pale vacuolated epithelial cells may be a protective device preventing an autoimmune response to sperm antigens in the context of toxicant-induced degeneration of the principal cells of the epididymal epithelium.