We have previously described a partial Drosophila cDNA, clone P19, which bears homology to members of the RNA recognition motif (RRM) family of proteins [Haynes et al. (1987) Proc. Natl. Acad. Sci. USA, 84, 1819-1823]. RNA binding as well as involvement in RNA processing has been demonstrated for some RRM proteins. We report here the further characterization of P19, which we renamed cabeza (caz). caz is located on the X chromosome at position 14B. Using Northern analysis, at least four transcripts from the caz gene were observed at varying levels during development. caz mRNA and protein are enriched in the brain and central nervous system during embryogenesis. In addition, the protein is enriched in the adult head. UV crosslinking was used to demonstrate in vitro RNA binding activity for full-length recombinant caz protein and for the caz RRM domain. Sequence analysis revealed caz is related to two human genes, EWS and TLS, which are involved in chromosomal translocations. The fusion of EWS and TLS to other cellular genes results in sarcoma formation. In addition to their overall structural organization and sequence similarity, these three genes share an RRM which is divergent from typical RRMs. Therefore, it appears that these genes constitute a new sub-family of RNA binding proteins.