We serially assayed soluble interleukin 2 receptor (sIL-2R) levels in the peripheral blood (PB) of 22 patients with rheumatoid arthritis (RA) followed for a period of 12 months, and correlated these levels with disease activity. We examined the relationship between the direction in which each of the disease measures changed between assessments and the direction of change in sequential sIL-2R levels. In 22 of the 25 (88%) instances where there was a 30% change in the active joint count between sequential assessments, the direction of change of the PB sIL-2R level was found to be in parallel (chi 2 = 11.7, p less than 0.008). Our results suggest that serial sIL-2R levels are a useful means of confirming clinically significant changes in disease activity in patients with RA, irrespective of therapy.