The protein products of proto-oncogenes possess functions (e.g., enzymatic activity) that play important roles in the cellular biochemical pathways which regulate normal cell growth and differentiation. While little is known abaout the biochemical functions of most proto-oncogene products, several are known to possess tyrosine-specific protein kinase activity. The most extensively studied of these tyrosine-specific protein kinases is pp60c-src. The product of the c-src proto-oncogene, pp60c-src, is the normal cellular homologue of the Rous sarcoma virus transforming gene, v-src, which encodes a closely related protein, pp60v-src. Both the v-src and c-src gene products are membrane-associated phosphoproteins which possess endogenous tyrosine-specific protein kinase activity. The transforming potential of pp60v-src and mutants of c-src appears to be related, in part, to the elevated specific activity of the v-src and mutated c-src encoded phosphotransferases. We have examined a variety of human tumor cell lines, human tumors and normal human tissues for pp60c-src tyrosyl protein kinase activity to determine the distribution and level of this enzymatic activity. The results of our studies demonstrate that pp60c-src protein kinase activity is significantly elevated in several apparently unrelated human cancers.