Previous studies have revealed that activation of rat striatal D₁ dopamine receptors stimulates both adenylyl cyclase and phospholipase C via G_s and G_q, respectively. The differential distribution of these systems in brain supports the existence of distinct receptor systems. The present communication extends the study by examining other brain regions: hippocampus, amygdala, and frontal cortex. In membrane preparations of these brain regions, selective stimulation of D₁ dopamine receptors increases the hydrolysis of phosphatidylinositol/phosphatidylinositol 4,5‐biphosphate. In these brain regions, D₁ dopamine receptors couple differentially to multiple Gα protein subunits. Antisera against Gα_q blocks dopamine‐stimulated PIP₂ hydrolysis in hippocampal and in striatal membranes. The binding of [³⁵S]GTPγS or [α‐³²P]GTP to Gα_i was enhanced in all brain regions. Dopamine also increased the binding of [³⁵S]GTPγS or [α‐³²P]GTP to Gα_q in these brain regions: hippocampus = amygdala > frontal cortex. However, dopamine‐stimulated binding of [³⁵S]GTPγS to Gαs only in the frontal cortex and striatum. This differential coupling profile in the brain regions was not related to a differential regional distribution of the Gα proteins. Dopamine induced increases in GTPγS binding to Gα_s and Gα_q was blocked by the D₁ antagonist SCH23390 but not by D₂ receptor antagonist l‐sulpiride, suggesting that D₁ dopamine receptors couple to both Gα_s and Gα_q proteins. Co‐immunoprecipitation of Gα proteins with receptor‐binding sites indicate that in the frontal cortex, D₁ dopamine‐binding sites are associated with both Gα_s and Gα_q and, in hippocampus or amygdala, D₁ dopamine receptors couple solely to Gα_q. The results indicate that in addition to the D₁/G_s/adenylyl cyclase system, brain D₁‐like dopamine receptor sites activate phospholipase C through Gα_q protein.