To identify genes induced in monocytes by interferon-gamma, we carried out PCR-based cDNA subtraction and subsequent differential display on mRNA isolated from a human monocytic leukemia cell line, THP-1. We detected a novel gene encoding a protein bearing GTP-binding motifs, the characteristics of GTP-binding proteins (G-proteins). We also identified the mouse homologue of this gene and designated the gene GP-1. The amino acid sequence of GP-1 deduced from the nucleotide sequence is highly conserved in human and mouse (97% identical over the entire protein), suggesting a fundamental physiological role for this molecule. As amino acid sequences of GTP-binding motifs of human and mouse GP-1 are practically identical to those of recently identified putative G-proteins of nematode, AGP-1 and CGP-1, these proteins are likely to be members of the same, novel G-protein family. GP-1 mRNA was readily detected in mouse brain, thymus, lung, and kidney, while GP-1 mRNA is rarely expressed in liver.