The aim of the present study was to examine the sensitivity to opioid-receptor agonists of mesenteric afferents supplying the small intestine and to characterize the subpopulations of any responsive fibres. Mesenteric afferent discharge was recorded electrophysiologically in response to cumulative doses (1-400 microgram kg-1) of the mu-receptor agonist [D-ala,2 N- me-Phe4, Gly5-ol]-enkephalin (DAMGO), the delta-receptor agonist [D-ala,2 D-leu5]-enkephalin (DADLE) and the kappa-receptor agonist U-50488. DAMGO and DADLE, but not U-50488, markedly stimulated whole nerve mesenteric afferent discharge (P < 0.05) that was unrelated to intestinal motor events. Subpopulations of afferent fibres responding to DAMGO were examined using waveform analysis to identify single units from within the whole mesenteric nerve bundles. One population was CCK-sensitive (15/15 fibres) and the other was a subpopulation of mechanosensitive afferents that responded to distension (17/28). 5-HT-sensitive afferents did not respond to DAMGO (0/11). We conclude that specific subpopulations of mesenteric afferents respond to mu- and possibly delta- but not kappa-receptor agonists. This sensitivity to opioids may contribute to the antinociceptive property of vagal afferents.