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We sought to investigate an influence of immunosuppressive drugs on acute phase response (APR) in rheumatoid arthritis (RA). Ninety-six patients (pts) were treated with methotrexate (MTX), or with cyclophosphamide (CTX) (9-intravenously, 19-orally), or with cyclosporin A (CSA). C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and alpha-1 antichymotrypsin (ACT) serum levels were measured by rocket immunoelectrophoresis. AGP and ACT microheterogenities evaluated using immunoelectrophoresis were expressed as reactivity coefficient (RC). Clinical improvement was observed in 71.4% MTX pts, 77.8% CTX intravenously pts, 36.8% CTX orally pts, 60.0% CSA pts. The number of side effects was the highest in CTX oral group (57.9% left the study). CRP, AGP, and ACT serum levels were increased in all groups of RA pts as compared to healthy controls. CRP level decreased only after MTX and CTX intravenous treatment. Moreover, a decrease in ACT was observed in CTX intravenously treated pts. AGP-RC was lower in the initial population of RA pts as compared to healthy control. After 6 months of treatment RC became significantly higher in MTX pts only. In opposite ACT-RC in RA pts was found to be elevated as compared to controls. After the treatment it fell down. The decrease was found to be significant only in pts treated with MTX. From our study we can conclude that MTX is the safest and the most effective agent among immunosuppressive drugs applied in RA. CTX given orally causes a number of adverse reactions, which frequently make continuous and effective treatment impossible. CTX intravenously and CSA are attractive in the treatment of the patients with severe and refractory RA. A lack of clinical benefit is reflected in the absence of acute markers changes.