In an effort to understand the role of protein kinase C (PKC) in nerve growth factor‐induced differentiation, we studied the expression of PKC using isoform‐specific antibodies. Western blot analysis on whole cell lysates showed that α,β∥,γ,δ,ϵ,ζ, ı/λ and μ were expressed in PC12 cells, except for θ which was absent. In nuclei obtained from control PC12 cells, small amounts of δ, ϵ, ı/λ and ζ were detected. A computer‐assisted search algorithm was used to search for the presence of bipartite nuclear targeting motifs. In classical PKC isoforms α,β∥,γ, two bipartite motifs were present, while atypical ı/λ and ζ‐PKC displayed one motif, whereas novel PKC isoforms did not exhibit any bipartite motif structure. Treatment of cells with differentiating doses of nerve growth factor (NGF) resulted in changes of differential magnitude for all of the nuclear PKC isoforms in response to NGF. However, little change in γ‐PKC was observed in response to NGF. This analysis indicated that other factors may contribute to transport of PKC into the nucleus, in addition to the bipartite motif itself. Atypical ζ‐PKC is required for NGF‐induced neurite outgrowth of PC12 cells (Coleman and Wooten: J Mol Neurosci 5:39–57, 1994). Increases in nuclear ζ‐PKC were NGF dose‐dependant with a concomitant decrease in cytoplasmic immunoreactivity. The localization of ζ‐PKC was investigated by means of immunoelectron microscopy which revealed the localization of this isoform within the inner nuclear matrix bound to chromatin. Taken together, these findings suggest that ζ‐PKC may be involved in the regulation of nuclear processes. J. Neurosci. Res. 49:393–403, 1997.