The aim of our study was to evaluate the effects of intra-articular methotrexate (MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or unique arthritic involvement of one knee, were treated with intra-articular injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte sedimentation rate (ESR). On the same days, an ultrasonographic examination of the involved knee was performed by two independent experienced operators. Synovial thickness in the suprapatellar bursa and the presence of joint effusion and Baker's cyst were assessed. An increase of the mean value of maximal knee flexion angle and a reduction of the mean values of ESR and VAS between T0, T9 and T17 were demonstrated. Ultrasonographic evaluation showed significant reduction of synovial thickness and joint effusion. No differences were detected for the presence of Baker's cyst. We may conclude that repeated intra-articular injections of MTX resulted in a decrease of local as well as systemic inflammatory signs. As far as we know, this is the first study that explores the effects of intra-articular MTX in RA and PsA both clinically and by ultrasonography.