Three types of opioid receptors mediate peripheral opioid antinociception in inflammation. Recently, antisera that recognize unique epitopes of the cloned mu-, delta-, and kappa-opioid receptors have been developed. Using these antisera we examined the regulation of opioid receptors in rat dorsal root ganglia after hindpaw inflammation and the influence of neurotoxins for primary afferent neurons and sympathetic neurons thereon. Peripheral tissue inflammation was produced by injection of complete Freund's adjuvant into the right hindpaw. Capsaicin was injected subcutaneously once a day for three days using a total dose of 150 mg/kg. 6-hydroxydopamine was injected intraperitoneally 75 mg/kg/day for three days. Freund's adjuvant induced a marked increase in the percentage of mu-, but a decrease in delta- and kappa-opioid receptor-positive neurons. Capsaicin significantly decreased mu-, delta- and kappa-opioid receptor immunoreactivity in both Freund's adjuvant treated and non-treated rats. No significant changes on the mu-, delta- and kappa-opioid receptor immunoreactivities were observed after 6-hydroxydopamine treatment in either Freund's adjuvant-treated or non-treated rats. Our studies indicate: (1) Peripheral inflammation can differentially regulate the expression of the three opioid receptors in dorsal root ganglia neurons with an up-regulation of mu- and down-regulation of delta- and kappa-opioid receptors. 2) A significant portion of mu-, delta- and kappa-opioid receptors are located on capsaicin-sensitive neurons in dorsal root ganglia of both non-inflamed and inflamed hindlimbs. 3) The expression of opioid receptors in dorsal root ganglia of either inflamed or non-inflamed hindlimbs is not influenced by sympathetic postganglionic neurons.