The c-erbB-2 gene is a v-erbB-related proto-oncogene which encodes a protein similar to but distinct from the epidermal growth factor (EGF) receptor. In situ hybridization of metaphase spread showed that this gene is located on human chromosome 17 at q21, a specific breakpoint observed in a translocation associated with acute promyelocytic leukemia. The c-erbB-2 DNA probe hybridized with a 4.6 kb mRNA which directs the synthesis of a 185 kd glycoprotein. The 185 kd c-erbB-2 protein is associated with tyrosine kinase activity and is possibly phosphorylated by C-kinase on its serine and threonine residues. In addition, the c-erbB-2 protein is suggested to be a substrate for EGF receptor tyrosine kinase, since EGF binding to the EGF receptor rapidly induced phosphorylation of the c-erbB-2 protein on its tyrosine residue. Southern blot hybridization analysis of DNAs from human tumors demonstrated amplification of the c-erbB-2 gene restricted to adenocarcinomas. Finally, the promoter of the c-erbB-2 gene contains the typical TATA box and CAAT box as well as a GC box-like sequence. This is in contrast with the promoter of the EGF receptor gene, since the latter contains only GC-boxes. Therefore, it is suggested that the two genes are under different transcriptional control.