The objective of this study was to analyse the anti-inflammatory and immunosuppressive properties of 6-hydroxydopamine (6-OHDA), a well known sympatholytic compound. Collagen type II arthritis, a T cell-dependent autoimmune disease, was significantly suppressed by a short-term administration of 6-OHDA at the time of the disease onset. Similar outcome was observed when in vivo models of T cell-dependent and independent inflammatory reactions were applied. In contrast, long-term pretreatment with 6-OHDA and hence efficient sympatholysis did neither affect the course of arthritis nor the outcome of T cell-dependent and independent inflammatory reactions. These findings, together with evidence of dose-dependent in vitro inhibitory effects of 6-OHDA on lymphocyte proliferation and differentiation, indicate that the anti-inflammatory features of this compound are mediated through a direct action on effector cells rather than by sympatholysis.