The extent of programmed cell death (apoptosis) which occurs upon transfer of a neuronal cell line (ND7) to serum-free medium can be greatly increased by addition of retinoic acid (RA) to the medium. Here we show that the degree of apoptosis can also be enhanced by agents which activate protein kinase C (PKC) and that such agents synergize with RA in inducing apoptosis. In contrast chronic down regulation of PKC dramatically reduces the ability of RA to induce apoptosis whilst ND7 cell lines selected for resistance to RA-induced apoptosis are also resistant to apoptosis induced by PKC activation. This indicates that a common death pathway mediates the induction of apoptosis by PKC activators and RA. The potential nature of this pathway and the role of PKC in neuronal cell apoptosis is discussed.