The Drosophila homolog of the vertebrate fibroblast growth factor receptor (FGF-R) was isolated by low-stringency hybridization. In contrast to the diversity of this subclass of receptor tyrosine kinases in vertebrates, the Drosophila genome appears to encode only a single homolog. Nucleotide sequence analysis demonstrates that the Drosophila FGF-R homolog (DFGF-R) protein has a conserved sequence, size, and organization. The extracellular region encodes three immunoglobulin-like domains, and the cytoplasmic kinase domain exhibits a high degree of similarity to the vertebrate FGF-Rs with the typical split kinase and comparably sized juxtamembrane and carboxy-terminal regions. The DFGF-R was mapped to position 70C on the third chromosome, and two overlapping chromosomal deficiencies that remove the gene were identified. Developmental Northern blots show that the gene has a single transcript of 4.3 kb and is expressed at all stages of development. Localization of the transcript and protein in embryos has shown that the gene is predominantly expressed in a restricted set of tissues: the developing tracheal system and the delaminating midline glial and neural cells. In embryos homozygous for a deletion of several genes including the DFGF-R locus, the initial formation of the tracheal pits is not affected. However, the extension of tracheal cell processes leading to the formation of the elaborate tree structure is blocked. The DFGF-R protein may thus participate in receiving spatial cues that guide tracheal cell outgrowth.