The recently discovered similarity between the human epidermal growth factor (EGF) receptor and the avian erythroblastosis virus v-erb-B protein supports the hypothesis that viral oncogenes share a common evolutionary origin with genes encoding growth-regulating cell-surface receptors. To elucidate the relationship between receptors and malignant transformation, we have now used a fragment of v-erb-B as a probe to screen a cDNA library of mRNA from A431 human carcinoma cells, which possess a large number of EGF receptors. Of the six clones isolated, the largest (pE7) contains an insert of 2.4 kilobase pairs (kbp) whose deduced amino acid sequence is homologous to the v-erb-B protein and identical to reported EGF receptor peptide sequences. This pE7 cDNA hybridized to three prominent RNAs of approximately 10, 5.6 and 2.9 kilobases (kb), and to three minor species of 6.3, 4.6 and 3.3 kb. All were present in elevated levels in A431 cells. The prominent 2.9-kb RNA was homologous only to the 5' portion of the pE7 insert. This result raises the possibility that differential RNA processing is used by A431 cells to generate a variety of RNAs.