The exposure of rat brain slices containing caudate putamen and accumbens nuclei to α-MSH or dopamine (DA) results in an increase in cyclic AMP (cAMP) levels. When tissues are compared with those containing both α-MSH and DA, a reduction in the cyclic nucleotide is observable. This study was carried out to determine whether variations in tissular cAMP levels induced by α-MSH might be explained by an interaction between the peptide and some dopaminergic receptors. Therefore, we measured cAMP in tissues and medium in response to α-MSH in the presence of haloperidol, the selective D 1 (SCH 23390) or D 2 (sulpiride) antagonists, or the selective D 1 (SKF 38393) or D 2 (bromocriptine) agonists. Haloperidol by itself induced no changes either in the cAMP content or in the cAMP efflux to the medium. When slices were exposed to α-MSH and haloperidol, the latter blocked the α-MSH effect of inducing an increase in the content of cAMP. None of the specific antagonists (at the administered doses) induced changes in the content of cAMP when compared with the control group. The presence of SCH 23390 in the incubation medium together with α-MSH yielded a reduction in cAMP levels compared with those incubated with α-MSH. A slight stimulatory effect on cAMP formation was observed when the dopaminergic agonists (SKF 38393 10 μM) were used. We conclude that α-MSH interacts with the D 1 dopamine receptor, changing the cAMP levels in striatum and accumbens nuclei.