From a Drosophila head cDNA library, we isolated 9 cDNA clones, each of which encodes a different member of Rab-protein family. Seven of them (DRabs) have more than 80% amino acid identity to the corresponding members of mammalian Rab proteins. The other two proteins (DRabRP3 and 4) show low sequence similarity to any of the known Rab proteins. However, both contain all amino acids conserved in known Rabs. In addition, DRabRP4 has strong GTP-binding activity, when synthesized in E. coli cells. These results indicate that DRabRPs are novel members of the Rab-protein family. Molecular phylogenetic analysis also supported this conclusion.