This study investigates the role of the opioid receptors and of the opioid peptide beta-endorphin in the development of yeast-induced inflammation in the rat paw. Pretreatment with the opioid receptor antagonist naltrexone (10 mg/kg i.p.) exacerbates the paw edema, while morphine pretreatment (5 and 10 mg/kg) reduces it. In addition, the intravenous injection of a specific anti-beta-endorphin antibody aggravates the yeast-induced inflammation. On the contrary, both the kappa-opioid receptor antagonist MR 1452(2.5, 5 and 10 mg/kg i.p.) and the delta-opioid receptor antagonist ICI 174-864 (2.5, 5 and 10 mg/kg i.p.) do not interfere with the inflammatory process. After intraplantar injection, naltrexone, morphine and the anti-beta-endorphin antibody do not interfere with the yeast-induced inflammatory edema. Our data suggest that beta-endorphin exerts an inhibitory regulation on the inflammatory responses through the activation of mu-opioid receptors probably located on immune cells, rather than in the paw.