Sequential daily measurements of erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) were performed for one week after an I.V. injection of 7.5-13 mg methotrexate (MTX) in 18 patients with rheumatoid arthritis. Early decreases of ESR and CRP were observed. Serum CRP was more sensitive than ESR, displaying more pronounced falls from baseline to both the minimal and to the 7th day levels. Patients receiving their first dose of MTX (n = 9) exhibited a more prominent reduction of CRP levels in comparison to veteran MTX users (n = 9). The prompt response of acute phase reactants to MTX may correspond to the relatively rapid clinical effect of the drug in RA. It may also support an antiinflammatory mechanism of action of low dose MTX.