aBSA arthritis was elicited by intraarticular (i.a.) injection of 60 micrograms aBSA into the knee joint of mice immunized with aBSA in Freund's complete adjuvant. The chronicity of the joint inflammation appeared to depend on the excellent charge-mediated retention of aBSA in the joint. We examined whether arthritis induced with the positively charged aBSA (pl approximately 8.5) could be modulated with the competitive polycation protamine (pl approximately 10). Concomitant i.a. injection of aBSA (60 micrograms) with protamine (180 micrograms) strongly reduced the aBSA arthritis. Lower dosages of protamine were less effective. Protamine caused a strong reduction in the retention of aBSA in the joint, particularly at the cartilage level. Our data indicate that protamine exerts its effect on aBSA arthritis by interfering with anionic retention sites in the joint.