Proto-oncogenes encoding growth factor receptors constitute several distinct families with close overall structural homology. The highest degree of homology can be observed in their catalytic domains, which are essential for intrinsic tyrosine kinase activity. Growth factor receptors in several of these families play critical roles in the regulation of normal cell growth and development. Some of these molecules have been implicated in the neoplastic process as well. A related DNA fragment distinct from epidermal growth factor receptor and erbB-2 genes was detected by reduced stringency hybridization of v-erbB to normal genomic human DNA. The expression of erbB-3 was studied by southern and northern blot technique in a subset of nine head and neck tumor cell lines, as well as in three immortalized cultures established from normal human salivary glands. No gene amplification of erb-B-3 was noted in any of the head and neck cell lines. The 6.2 kb transcript of erbB-3 was elevated significantly in an epidermoid carcinoma of the larynx (A388) and an esophageal carcinoma (HA 114).