Parkinson’s disease, has been shown to have anti-inflammatory activity in the carrageenan paw edema assay in rats at po doses greater than or equal to 0.3 mg/kg. Studies were done to investigate the mechanism of action and to determine the pharmacologc significance of this finding. Because pergolide elevates circulating glucocorticoids, the effect of pergolide on carra-geenan-induced paw swelling was assessed in adrenalectomized rats. Pergolide retained its anti-inflamatory activity in adrenalec-tomized carrageenan-injected rats, thus eliminating corticoster-one induction as a possible mechanism of action. Pergolide treatment also did not decrease thromboxane B2, prostaglandin E2 or leukotriene B4 production, ruling out direct effects on araChadonic acid inflammatory mediators. Interactions with the autonomic nervous system were suggested, in that an alpha adrenergic agonist (clonidine) mimicked the activity of pergolide in the carrageenan assay, and an alpha adrenergic antagonist (phenoxybenzamine) blocked the anti-inflammatory activity of pergolide in this assay. Dopamine receptor antagonists(haloper-idol or sulpinde) partially inhibited the effect of pergolide in the carrageenan model. However, the peripherally restricted dope-mine antagonist, dompendone, was ineffective, suggesting that a central dopamine receptor was involved in the effect. Experiments in chronic inflammation models such as lipoidal-amine induced arthritis in rats and picryl ChlOride-indUCed delayed type hypersensitivity in mice also revealed an anti-inflammatory effect of pergolide. Activity in the carrageenan system and the lipoidal-amine model demonstrated that the anti-inflammatory effects of pergolide were separable from potential immunosuppressive ef-fects. Multiple dose studies indicated that tolerance might de-velop to the anti-inflammatory effect of pergolide. Results of these studies indicated that treatment of rats with pergolide resulted in nonimmunologically mediated anti-inflammatory activ-ity that was not a result of corticosterone induction or decreased production of arachidonic acid metabolites. Rather, the anti-inflammatory effect seemed to be dependent upon effects on the sympathetic nervous system.