Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.