Although corticosteroids (CS) cause nitrogen wasting in healthy humans, it is not known whether the salutary antiinflammatory and appetite-stimulating effects of CS in inflammatory diseases mitigate this effect. We measured nitrogen balance before, during, and after 3 d of high-dose methylprednisolone therapy in nine patients with flare-ups of rheumatoid arthritis. There was evidence of preexisting somatic protein and fat depletion in seven of nine subjects. Patients were allowed to eat freely on a metabolic ward. Nitrogen balances were -0.89 +/- 1.38 g/d (means +/- SEM) before CS therapy, -5.77 +/- 1.30 g/d during therapy (P less than 0.001), and -3.54 +/- 1.38 g/d after therapy (P less than 0.01) despite increased energy and nitrogen intake and clinical resolution of inflammation during and after the pulse therapy. We conclude that patients with rheumatoid arthritis are often cachectic and high-dose CS cause nitrogen wasting in these patients despite an antiinflammatory and appetite-stimulatory benefit.