Antisera were produced against synthetic peptides predicted from the recent cloning of a delta opioid receptor, DOR-1. Confocal microscopic examination of immunostained spinal cord sections revealed that DOR-1 immunoreactive (-ir) nerve fibers and terminals form a moderately dense plexus within the superficial dorsal horn of rats and mice. These fibers decreased dramatically following dorsal rhizotomy and consistent with these observations a population of small diameter neurons in ganglia exhibited DOR-1-ir. DOR-1-ir ganglion neurons were also immunoreactive for calcitonin gene-related peptide (CGRP), and their terminals in the spinal cord contained both CGRP- and DOR-1-ir, the latter presumably located as a 'presynaptic' receptor. Interestingly, terminals containing DOR-1-ir appeared to be closely apposed by fibers and terminals containing enkephalin (ENK)-ir, which suggests that ENK may be a physiologically relevant ligand for the receptor encoded by DOR-1, and that DOR-1 may act to regulate the release of transmitters from small diameter primary afferent neurons.