Interactions between central opioids and catecholamines are thought to underlie the ability of adrenergic agonists both to lower blood pressure and alleviate certain symptoms of opiate withdrawal. We examined the cellular substrate for interactions between neurons containing enkephalin-like opioid peptides and catecholamines in cardiovascular portions of the medial nuclei of the solitary tracts (m-NTS) of adult rats. Single sections were dually labeled using a double-bridged peroxidase method for the localization of a monoclonal leucine (Leu5)-enkephalin-antibody and immunoautoradiography for the localization of polyclonal antibodies against the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Light microscopy revealed a few perikarya and numerous varicosities containing Leu5-enkephalin-like immunoreactivity (LE-LI). These were distributed among TH-labeled perikarya and processes throughout the rostrocaudal NTS. Electron microscopy of the m-NTS at the level of the area postrema further established the single as well as dual localization of TH and LE-LI in individual perikarya, dendrites, and axon terminals. Silver grains indicative of TH-labeling were usually distributed throughout the cytoplasm, whereas the peroxidase reaction product for LE-LI was localized principally to large (80-150 nm), dense-core vesicles. Immunoautoradiographic labeling for TH was detected in 118 terminals within a series of sections containing 183 terminals with LE-LI. Of these, 26% of the TH-labeled terminals and 32% of the enkephalin-containing terminals formed symmetric synapses with unlabeled dendrites, while only 7% of each type formed symmetric synapses with TH-labeled dendrites. In favorable planes of sections, the unlabeled as well as TH-labeled dendrites received convergent input from both types of terminals. A few of the remaining terminals that contained either TH or LE-LI formed asymmetric junctions with unlabeled distal dendrites; the others were without recognizable synaptic specializations within the plane of section. Approximately 20% of the TH-labeled terminals and 6% of the terminals containing LE-LI were dually labeled for both antibodies. These were invested with astrocytic processes characterized by bundles of intermediate filaments. We conclude that within cardiovascular portions of the m-NTS, opioid peptides and catecholamines contained within the same or separate terminals modulate the activity of target neurons through direct symmetric, probably inhibitory, synaptic junctions and may additionally modulate the activity of neighboring astrocytes through exocytotic release from large dense-core vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)