Single- and double-labeling immunocytochemical staining procedures were used to examine the relationship between adrenocorticotropin (ACTH)-containing nerve terminals and dopaminergic (DA) neurons in the rat midbrain, using both light and electron microscopy. At the light microscopic level, ACTH neuronal processes were found largely in restricted regions occupied by the mesolimbic and mesocortical DA neurons. At the electron microscopic level, in the central linear nucleus, ACTH axon terminals made symmetric and asymmetric synaptic contacts with DA dendrites, as well as appositions with unlabeled axon terminals which, in turn, synapsed upon DA dendrites. These data suggest that ACTH functions as a neurotransmitter/neuromodulator in the brain, and such ACTH-DA synapses may be important for stress-induced changes in mesocorticolimbic DA neuronal activity.