The susceptibility of cortical neurons to two forms of apoptotic death was compared with susceptibility to excitotoxic death during development in vitro (DIV 4-21). Murine cortical cultures were exposed for 48 h to the phosphatase inhibitor cyclosporine, the protein kinase inhibitor staurosporine or the excitotoxin N-methyl-d-aspartate (NMDA). Susceptibility to apoptosis induced by staurosporine or cyclosporine was maximal between DIV 4-10 and declined from DIV 10 through 18. The opposite pattern was observed with susceptibility to NMDA receptor-mediated excitotoxic necrosis, which was minimal at DIV 6 and progressively increased through DIV 21.