G(olf) alpha is a G-protein originally believed to mediate signal transduction exclusively within the olfactory neuroepithelium and subsequently found to be a major stimulatory G-protein in the basal ganglia. Here we present evidence that G(olf) alpha is expressed in several other tissues. The human isoform of G(olf) alpha was isolated from two human insulinoma cDNA libraries. Comparison of the human sequence with rat G(olf) alpha shows 91% nucleotide identity (within the coding region) and 99% identity at the amino acid level. Northern and reverse transcriptase-polymerase chain reaction analyses indicated that G(olf) alpha is expressed in all human insulinomas examined thus far as well as in normal pancreatic islets. G(olf) alpha mRNA was also detected in testis, retina, brain, and liver. Western blot analysis of various mouse tissues demonstrated that the level of G(olf) alpha protein in islets is lower than that in the olfactory neuroepithelium and other parts of the brain; its expression in retina, lung, and spleen was moderately higher than that in islets, and its expression in testis approached that in olfactory neuroepithelium. G(olf) alpha was also detected by immunohistochemistry in mouse islets, human insulinomas, the epithelial lining of mouse epididymis, photoreceptor cells of mouse retina, and mouse lung alveoli. These findings suggest a role for G(olf) alpha in a diverse population of cells located outside the olfactory neuroepithelium and central nervous system.