Polyarthritis induced by inoculation with complete Freund's adjuvant alters opioid peptides, but does not affect opioid receptor binding. This study was conducted to measure mu and delta opioid receptor-stimulated G-protein activity in brain and spinal cord of rats 19 days after injection of complete Freund's adjuvant or vehicle. Mu and delta opioid-stimulated [ 35 S]GTPγS binding measured autoradiographically in caudate–putamen, medial thalamus and periaqueductal gray was unchanged in polyarthritic rats. Delta opioid-stimulated [ 35 S]GTPγS binding was significantly decreased in the spinal cord of polyarthritic rats, whereas mu opioid-stimulated activity was unchanged. These data reveal that the functional activity of delta opioid receptors in the spinal cord is altered in polyarthritis.