Enhanced delta opioid receptor transmission may represent an endogenous compensatory mechanism in parkinsonism to reduce the activity of the indirect striatopallidal pathway following dopamine depletion. Furthermore, increased delta opioid receptor transmission may be causative in the production of dyskinesia following repeated dopaminergic treatment in Parkinson's disease. The present study employed radioligand receptor autoradiography, using [ 3 H]naltrindole, a ligand selective for the delta opioid receptor, to assess delta opioid receptor binding sites in forebrain regions of reserpinetreated rats, and in parkinsonian nondyskinetic, and dyskinetic MPTP-lesioned macaques. In reserpine-treated animals, specific delta opioid binding was increased in premotor cortex (ฯฉ30%), sensorimotor striatum (ฯฉ20%), and associative stri-atum (ฯฉ17%) rostrally, but was not changed in caudal forebrain. In contrast, delta opioid receptor binding was not significantly altered at any region analyzed, in either nondyskinetic or dyskinetic, MPTP-lesioned macaques, compared to normal. These results suggest that transient changes in delta opioid receptor binding may occur in motor circuits following acute dopamine depletion. However, in the more chronic MPTPlesioned macaque model, simple changes in delta opioid receptor number or affinity are unlikely to contribute to mechanisms for abnormal opioid transmission in Parkinson's disease and dyskinesia.