To study the role of cellular immunity in recent-onset rheumatoid arthritis (RA), 26 patients with early RA were examined by skin testing with seven common recall antigens. The skin test was performed before the administration of second-line antirheumatic therapy and was repeated after six months of medication. Controls included healthy individuals and patients without known immunological abnormalities or malignancies. 50% of the RA patients were classified as anergic compared to 7% of the controls. In the RA patients, depression of cell-mediated immunity was related to gender but not to disease activity. Anergic and reactive patients showed similar clinical improvement after six months of therapy. The frequency of anergy at six months was not statistically different from that before therapy. HLA-DR4 was more frequent in the reactive patient group (92%) compared with anergic patients (53%). We conclude that cell-mediated immunity is impaired in early RA but the impairment does not correlate with disease activity or with the response to treatment and does not return to normal during treatment with second-line antirheumatic drugs.