In a randomized, prospective study the efficacy and tolerability of extensive multiple intra-articular administrations of two antibiotics, rifamycin SV and pefloxacin, were evaluated in 40 patients with classical or definite rheumatoid arthritis. Total weekly doses of 525 mg rifamycin or 560 mg pefloxacin were given for 10 weeks, and 12 months after treatment all clinical indices, erythrocyte sedimentation rate and C-reactive protein improved significantly in the rifamycin group. Some of the treatment indices (morning stiffness, severity of pain by visual analogue scale, grip strength and Ritchie's index) were already improved when the treatment ended, whereas others (erythrocyte sedimentation rate, C-reactive protein, number of painful and swollen joints) improved progressively during the follow-up. In the pefloxacin treatment group all indices except C-reactive protein and severity of pain determined using a visual analogue scale were significantly improved 12 months after treatment. Comparison of the two treatments showed a significant difference in erythrocyte sedimentation rate (P less than 0.047), Ritchie's index (P less than 0.036) and C-reactive protein (P less than 0.028) in favour of rifamycin.