Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.