Evidence has accumulated to implicate neuropeptides localized within midbrain dopamine neurons (cholecystokinin, neurotensin, acetylcholinesterase) in synaptic transmission, mental disease, and pharmacotherapy. We suggest a means by which antipsychotic drugs alter the dynamics between dopamine and colocalized peptides: the intrinsic ability of these agents to stimulate dopamine neuronal activity while blocking dopamine receptors modulates the ratio of catecholaminergic to peptidergic transmission within the mesotelencephalic system. Imbalances of peptide and dopamine cotransmission and their modulation by neuroleptics may be relevant to the pathogenesis and pharmacotherapy of schizophrenia.