Differential hybridization of a cDNA library from rat pheochromocytoma PC12 cells with cDNA probes from naive PC12 cells and from PC12 cells exposed to nerve growth factor for 7 days identified cDNA sequences of two genes induced by NGF. The mRNA species detected by these cDNA sequences, designated 42A and 42C, reached maximal levels after 24 hr of treatment with NGF and were still significantly higher than control levels after 7 days. Epidermal growth factor transiently induced both mRNAs but at much lower levels. The mRNAs code for 95- (42C) and 101- (42A) amino acid residue peptides whose sequences are homologous to those of a family of calcium-binding proteins including the S-100 protein. The conservation of primary and secondary structure between 42A, 42C, and the other proteins suggests a possible role for them in the regulation of cell growth and differentiation.