Unilatera1 lesions of the substantia nigra were made with 6-hydroxydopamine in rats. In this model, drugs such as naloxone, which block endogenous enkephalin receptors, potentiated agents with postsynaptic dopaminergic actions, while antagonizing agents with presynaptic dopaminergic actions. Drugs which increase brain enkephalin content (d-phenylalanine or methionine-enkephalin) antagonized postsynaptically active agents and potentiated presynaptic agents. Naloxone also reversed reserpine-induced parkinsonism in rats. Separate pre-and postsynaptic enkephalinergic neurons thus seem to modulate nigrostriatal function.