A unique gene termed DER (Drosophila epidermal growth factor [EGF] receptor homolog) was isolated from Drosophila melanogaster and mapped to position 57F on the right arm of the second chromosome. The deduced amino acid sequence showed that the DER protein is 1409 amino acids long. In homology it is similar to the human EGF receptor and to rat and human neu proteins. The most striking difference between the Drosophila and human homologs is DER's additional 166 amino acids. The extra sequence is rich in cysteine residues and is another duplication of one of the two cysteine-rich regions, which are a hallmark of the EGF receptor and related proteins. Analysis of several cDNA clones of DER revealed variability at the 5' end of the coding region, demonstrating the presence of at least three splicing alternatives. All three transcripts have a similar tissue distribution during development: they are uniformly distributed in embryos, localized primarily in proliferating tissues in larvae, and found mainly in the brain cortex and the thoracic and abdominal ganglia in adults. The DER protein thus seems to have multiple roles during development, and it may represent a "universal" transducer of signals into the cell.