Protein, mRNA and activity levels of the calcium-independent protein kinase C (nPKC) isoenzymes were examined in NG108-15 cells. Western blot analyses reveal that proliferating NG 108-15 cells express the delta, epsilon, and eta, but not the theta species. The atypical species PKC zeta was also detected. Differentiation of these cells with dibutyryl cAMP was associated with increase in the levels of PKC epsilon, with no significant changes in its steady-state mRNA levels. The levels of the other isoforms were not altered by the differentiated state. Similarly, no changes in nPKC activity were discerned in either the soluble or particulate fractions when histone or other proteins were used as substrates. These data suggest that the PKC epsilon isoform may be important for the production and maintenance of the differentiated state in NG 108-15 cells.