All neurotransmitter and hormone receptors that stimulate adenylyl cyclase are thought to do so via the alpha subunit of the guanine nucleotide binding (G) protein G(s). The basal ganglia contain a well-characterized dopamine-stimulated adenylyl cyclase and D1 dopamine receptors coupled to G(s) are thought to mediate this activity. We have found using immunohistochemistry, immunoblotting, and cholera toxin-dependent ADP ribosylation that the rat basal ganglia contain very high levels of a G(salpha)-like protein; however, it is distinct from the G(s) in other brain regions. Furthermore, in situ hybridization and Northern blot studies showed that the striatum contains remarkably low levels of G(salpha) mRNA. G(olf) is a G protein recently cloned from olfactory sensory neurons which can also stimulate adenylyl cyclase. We have now discovered high levels of G(olf) mRNA expression in the striatum, nucleus accumbens, and olfactory tubercle. Northern blot analyses indicate that in the striatum, G(olf) transcripts are approximately 10-fold more abundant than G(salpha) transcripts. Thus G(olf) is not an olfactory neuronspecific G protein. It is also the major stimulatory G protein in the basal ganglia, where it may couple D 1 dopamine receptors to adenylyl cyclase.