It is widely accepted that temperature regulates gene expression and function in the epididymis. However, the significance of reduced temperature of the scrotum in cell survival had not often been examined. Our hypothesis was that the experimental increase of the temperature could induce apoptosis. Using a surgical method that consists of surgically reflecting the cauda epididymidis in the abdomen, we have been able to show that this is the case. Apoptosis was examined by histologic procedures and by visualization of DNA fragmentation in agarose gels. We determined that the apoptosis is region-specific and affects only the principal cells of the proximal region of the cauda. It starts 12 h after surgery and ends by the third day. The apoptotic cells are eliminated by extrusion into the lumen and phagocytosis by adjacent cells. The complete molecular mechanism of apoptosis in this case remains unknown, but we have used the techniques of immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction to determine the role of some molecules. We have seen no significant role of androgens, the tumor suppressor p53, nor two heat shock proteins, hsp-25 and hsp-70. Nevertheless, we have detected a strong induction of bax and bcl-2 gene products. While the former should be responsible for the apoptosis observed, the latter would promote the survival of most of the cells of the cauda epididymis.