To compare the efficacy and tolerability of single-agent sulfasalazine (SSZ) with combination therapies composed of SSZ and methotrexate (MTX) and SSZ, MTX and hydroxychloroquine (HCQ) in active spondyloarthropathy (SpA) patients with peripheral arthritis.One hundred and fifty SpA patients with peripheral arthritis (male/ female: 92/58) who were treated in our clinic between 1994 and 1998 were enrolled in this trial. Patients treated with SSZ alone (1-3 gr/day) were included in Group I, patients treated with combination of SSZ (1-3 gr/day) and MTX (7.5-15 mg/week) in Group II, and patients treated with combination of SSZ (1-3 gr/day), MTX (7.5-15 mg/week) and HCQ (200 mg/day) in Group III. Forty-eight patients in Group I, 45 patients in Group II and III were eligible for statistical analysis at the end of study.The combination of MTX, SSZ, and HCQ, and the combination of MTX and SSZ were more effective regarding the clinical and laboratory parameters than SSZ alone (p<0.05). Moreover, the combination of MTX, SSZ, and HCQ was more effective than the combination of MTX and SSZ (p<0.05).Combination therapies seem to be more effective and no more toxic than monotherapy in SpA patients with peripheral arthritis.