In the brain, dopamine and adenosine stimulate cyclic AMP (cAMP) production through D1 and A2a receptors, respectively. Using mutant mice de®cient in the olfactory isoform of the stimulatory GTP-binding protein a subunit, Ga olf , we demonstrate here the obligatory role of this protein in the adenylyl cyclase responses to dopamine and adenosine in the caudate putamen. Responses to dopamine were also dramatically decreased in the nucleus accumbens but remained unaffected in the prefrontal cortex. Moreover, in the caudate putamen of mice heterozygous for the mutation, the amounts of Ga olf were half of the normal levels, and the ef®cacy of dopamine-and CGS 21680 A 2 agonist-stimulated cAMP production was decreased. Together, these results identify Ga olf as a critical parameter in the responses to dopamine and adenosine in the basal ganglia.