Bcl6 protein has been detected in testicular germ cells, mainly spermatocytes, of normal mice, but its physiological role is largely unknown. The number of spermatozoa in the cauda epididymis of adult Bcl6-deficient (Bcl6−/−) mice is lower than that of Bcl6+/+ mice. We have found numerous apoptotic spermatocytes at the metaphase I stage with induction of Bax protein in adult Bcl6−/− testes. Developmentally, the incidence of germ cell apoptosis of Bcl6−/− mice was similar to that of Bcl6+/+ mice until six weeks of age and increased after eight weeks of age. The incidence of apoptosis in heterozygous Bcl6+/− mice was also higher than that of Bcl6+/+ mice. Since the activated form of p38 MAP kinase was detected in spermatocytes of adult Bcl6−/− mice, the germ cell apoptosis may be induced by stressors. Treatment of testes of adult Bcl6+/+ mice with a mild hyperthermia resulted in germ cell apoptosis predominantly in metaphase I spermatocytes with induction of Bax protein and activation of p38 MAP kinase and this apoptosis mimics that in adult Bcl6−/− mice. Thus, Bcl6 may play a role as a stabilizer in protecting spermatocytes from apoptosis induced by stressors.