Recent reports indicate that the protein kinase inhibitor H7 is capable of inducing both morphological and functional differentiation of a number of neural cell types. This investigation demonstrates that H7 potentiates the neurogenic properties of nerve growth factor (NGF) in PC12 cells with a concomitant change in the accumulation of the beta II-protein kinase C (beta IIPKC) isoform protein without changes in either alpha or gamma. However, NGF alone stimulates a coordinate increase in all three isoforms. The assay of acetylcholine esterase as a functional marker of neuronal differentiation demonstrates that H7 alone is not capable of stimulating morphological or functional differentiation in PC12 cells. H7 synergizes with NGF through a PKC-dependent pathway and by differential expression of PKC subtypes. The expression of the PKC transcripts for alpha, beta II, and gamma all undergo simultaneous yet differential changes in their patterns of expression during treatment with H7 and/or NGF. These data suggest that isoform switching is regulated primarily at the protein level. Last, these findings suggest that expression of PKC isoforms is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state.