We used the whole cell open-patch or perforated-patch technique to characterize µ-opioid modulation of Ca²⁺ current (I_Ca) in nodose sensory neurons and in a specific subpopulation of nodose cells, aortic baroreceptor neurons. The µ-opiate receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO) inhibited I_Ca in 95% of neonatal [postnatal day (P)1-P3] nodose neurons. To the contrary, only 64% of juvenile cells (P20-P35) and 61% of adult cells (P60-P110) responded to DAGO. DAGO-mediated inhibition of I_Ca was naloxone sensitive, irreversible in the presence of guanosine 5'-O-(3-thiotriphosphate), absent with guanosine 5'-O-(2-thiodiphosphate), and eliminated with pertussis toxin; DAGO's inhibition of I_Ca was G protein mediated. Incubation of neurons with -conotoxin GVIA eliminated the effect of DAGO in neonatal but not in juvenile cells. In the latter, DAGO reduced 37% of the current remaining in the presence of -conotoxin. In the subset of nodose neurons, aortic baroafferents, the effect of DAGO was concentration dependent, with an IC₅₀ of 1.82 × 10⁸ M. DAGO slowed activation of I_Ca, but activation curves constructed from tail currents were the same with and without DAGO (100 nM). In summary, µ-opiate modulation of I_Ca in nodose neurons was demonstrated in three age groups, including specifically labeled baroafferents. The demonstration of a mechanism of action of µ-opioids on baroreceptor afferents provides a basis for the attenuation of the baroreflex that occurs at the level of the nucleus tractus solitarii.