Opioid and D-2 receptor agonists inhibit adenylate cyclase activity in neostriatal slices and homogenates. In the present study we used cyclic AMP efflux from rat neostriatal tissue as a parameter to estimate the effects of these drugs on cyclic AMP formation. Both the mu-opioid receptor agonist morphine and the D-2 dopamine receptor agonist LY 171555 were able to inhibit the forskolin-stimulated cyclic AMP efflux. The effects of morphine and LY 171555 could be reversed by naloxone and sulpiride, respectively. These data indicate that measurements of cyclic AMP efflux from brain slices is an accurate reflection of the effects of receptor stimulation on adenylate cyclase activity.