FK506 is an immunosuppressive drug that binds to FK506 binding protein (FKBPs), a subgroup of cytosolic proteins called immunophillins. Previous works have revealed that FK506 protects neural cells from ischemia or excitotoxicity. Here we report that FK506 (10(-6) M) and not cyclosporine A (10(-6) M) blocks neuronal apoptosis induced by serum deprivation in rat neuronal cultures. In addition the immunohistochemical staining of C-jun protein in deprived cultures is markedly attenuated by FK506. The proportion of C-jun-positive neurons in control cultures, in serum-deprived cultures (48 h) and in serum-deprived cultures exposed to FK506 (10(-6) M) were 12.5%, 56.5% and 16.5%, respectively. The down-regulation of C-jun could play a major role in the anti-apoptotic action of FK506 in stressed neuronal cultures.