New interest in the use of antibiotics in the treatment of arthritis was stimulated by two factors: (1) observations that, in some forms of chronic arthritis, microbial antigens persist in the synovial membrane, and (2) the increasing knowledge of the anti-inflammatory and immunosuppressive effects of antibiotics. Recently, several published controlled studies reported a beneficial effect of tetracyclines on RA and reactive arthritis. Whether the anti-arthritic activity of the tetracyclines investigated is mediated by the antimicrobial, anti-inflammatory or immunomodulatory properties remains to be determined. It may be concluded from these studies that tetracyclines have a beneficial effect on RA, especially when laboratory parameters are considered. The effect on the clinical parameters is not unequivocal. The adverse effects seem to be mild but the long-term efficacy and safety of tetracyclines as disease-modifying antirheumatic drugs remain to be demonstrated.