OBJECTIVE: To evaluate the associations of soluble serum interleukin-2 receptor (sIL-2R) levels in patients with rheumatoid arthritis (RA) with clinical and laboratory measures of disease activity and the predicted response to therapy. METHODS: sIL-2R levels were determined by ELISA in 137 patients with RA, not previously treated with 2nd line therapy. Patients were enrolled in a prospective, randomized, placebo controlled trial of sulfasalazine (SSZ) versus gold sodium thiomalate (GSTM), sponsored by the Cooperative Systematic Studies of Rheumatic Diseases. Using correlation analysis and regression modeling, the clinical utility of sIL-2R as a measure of disease activity and predictor of outcome was assessed. RESULTS: 91 women and 46 men with a mean age of 51 +/- 13 years and mean duration of disease of 64 +/- 78 months participated in this study. The mean sIL-2R level in all patients with RA was markedly elevated (980 +/- 589 U/ml) compared with that in healthy control subjects (446 +/- 196 U/ml; p = < 0.0001). There was no correlation between the sIL-2R levels and the joint pain/tenderness count, either at study entry or completion. There were significant positive correlations between the baseline sIL-2R and baseline erythrocyte sedimentation rate (ESR) and between the change in sIL-2R and the change in ESR. Both a multiple linear regression model and a multiple logistic regression model showed that baseline sIL-2R levels were not predictive of clinical outcome. CONCLUSION: sIL-2R levels are significantly elevated in patients with active RA and correlate positively with ESR. However, these results indicate that in patients with early RA, sIL-2R levels are neither associated with standard disease activity criteria nor predictive of the response to therapy with SSZ or GSTM, even after controlling for the simultaneous effects of other important clinical variables.