An affinity-purified anti-peptide antibody generated against the carboxy-terminal region of the delta opioid receptor was used to localize delta opioid receptors in mouse brain. delta Opioid receptor immunoreactivity was found in axons and nerve terminals in regions of the olfactory bulb, hippocampal formation, cerebral and cerebellar cortex, midbrain and hindbrain. The immunocytochemical distribution correlated well, though not completely with autoradiographic distribution of delta opioid receptors in mouse brain using either [3H][2-D-penicillamine, 5-D-penicillamine]-enkephalin (DPDPE) or [3H]naltrindole. Confocal microscopy of double-labeled tissue provided direct evidence that delta opioid receptors are principally expressed on GABAergic terminals in the hippocampus. These anatomical findings complement extensive physiological studies to provide a more detailed description of endogenous opioid circuitry.