Advances since my last review in 1998 on our understanding of the effects of heat on the testis are summarized. Techniques used to study these effects have included exposing the whole animal to a hot environment, insulation of the whole scrotum or just its neck, immersing the testes in a warm water bath, surgically returning one or both testes to the abdominal cavity (induced cryptorchidism) or exposing them to microwave radiation. Most techniques have been shown to affect principally primary spermatocytes and early spermatids, but there is some evidence for effects on spermatogonia and Sertoli cells. The Leydig cells and androgen secretion do not appear to be directly affected. There is considerable variation in susceptibility between individual animals and between different strains, which appears to be due to differences in the ability of the animals to maintain testis temperature as well as in inherent susceptibility of the different germ cells. The mechanism of cell death appears to be apoptosis, not necrosis, and may involve reactive oxygen species (ROS), the tumour suppressor protein p53, nitric oxide synthase (NOS), the translocation of the proapototic factor Bax from the cytoplasm to a perinuclear position, the release of cytochrome c from mitochondria and several caspases. Animals deficient in Fas and Fas ligand appear still to be susceptible, making it unlikely that these factors are involved. Although many authors believe that the effects of heat are fully reversible, there is now evidence of long-term effects, following either locally applied heat or temporary induced cryptorchidism. These long-term effects appear to be different from those seen following irradiation, and may indicate a failure of Sertoli cell function. Sperm produced by mice which had been exposed to a hot environment bind to ova normally but are less able to fertilize in vivo and in vitro, even when motile sperm are selected by a swim-up procedure, and many of the resultant embryos do not develop normally. Blocking caspase activity or release of cytochrome c reduced the effect of heat. Mice lacking iNOS were more resistant to the effects of local testicular heating, and inhibitors of xanthine oxidase (an enzyme important in the production of ROS) reduced the effects of making the testis cryptorchid, while mice in which the gene for superoxide dismutase (SOD1, which is involved in the breakdown of ROS) had been knocked out were more sensitive. Treatment of rats with pregnant mare serum gonadotropin, thyroxin or low doses of testosterone increased the time at which infertility began following testicular heating. Treatment with vitamin E or PBN (Ntert-butyl-α−phenylnitrone, a free radical spin trap but also a possible source of NO) decreased the effects of local testicular heating on testis weight, while ascorbic acid had no effect; in contrast treatment with PBN increased the effect of temporary induced cryptorchidism. The most surprising finding was that induced cryptorchidism actually improved spermatogenesis in juvenile spermatogonial depletion (jsd) mice and to some extent in previously irradiated mice and rats treated with hexanedione