Rat striatal adenylate cyclase stimulated with combinations of 100 microM dopamine plus 40-100 nM forskolin was inhibited to a significantly greater extent by the muscarinic agonist carbachol than was forskolin-stimulated activity in the absence of dopamine. In the presence of Ro 201724 as phosphodiesterase inhibitor, a 100 microM concentration of the adenosine agonist 2-chloroadenosine stimulated adenylate cyclase activity 6.6 -fold over basal activity. In contrast to dopamine-stimulated activity, carbachol did not significantly inhibit adenylate cyclase activity elevated by the adenosine agonist, indicating specificity of the muscarinic response for dopamine stimulation. The effects of muscarinic antagonists on striatal versus heart adenylate cyclase indicated that the striatal response was mediated primarily through M4 receptors. The present results suggest that muscarinic M4 and dopamine D1 receptors are co-localized and functionally coupled in rat striatum.