It is known that PKC is differently expressed in brain and the peripheral nervous system and is involved in cellular differentiation. We have analyzed 9 human neuronal-derived crest-cell lines for PKC-alpha mRNA. Seven out of nine expressed 9.0 kb and 4.0 kb PKC-alpha mRNAs, but three had high level of 9.0 kb transcription. The different expression of the two messenger RNAs may result from alternative splicing and a different degree of cell maturation. The same cell lines were studied for MYCN gene expression. A possible relation between the two genes is discussed. One cell line expressing high levels of both PKC-alpha mRNA was treated with 10(-5) M retinoic acid (RA). The expression of both messenger RNAs was suppressed when the cells achieved a morphological differentiation and showed neurite-like processes. A decrease of PKC-alpha gene expression was associated to down regulation of MYCN mRNA. These preliminary results suggest that PKC suppression of PKC-alpha mRNA is associated with reversion of the malignant phenotype.