We investigated soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and soluble intercellular adhesion molecule-1 (sICAM-1) levels in the sera of patients with non-malignant diseases believed to have an autoimmune or immunosuppressive component, Crohn's disease, celiac disease, and systemic lupus erythematosus (SLE). Sera of healthy blood donors served as controls. All samples were analyzed by commercial ELISA kits for sIL-2R, sCD8, and sICAM-1. Our control level of sIL-2R (x +/- S.D) was 395 +/- 84 units/ml, sCD8 (x +/- S.D.) 263 +/- 90 units/ml and sICAM-1 405 +/- 118 ng/ml. The 8 Crohn's disease patients had an average sIL-2R level of 920 +/- 329 units/ml, and an average sCD8 level of 355 +/- 91 units/ml, and sICAM-1 952 +/- 329 ng/ml. The four celiac disease patients had an average sIL-2R concentration of 1740 +/- 1071 units/ml, a sCD8 level of 460 +/- 320 units/ml and sICAM-1 1221 +/- 720 ng/ml. The three systemic lupus erythematosus patients had an average sIL-2R of 1023 +/- 123 units/ml, and an average sCD8 of 395 +/- 69 units/ml, and sICAM-1 1153 +/- 219 ng/ml. Thus, sIL-2R and sICAM-1 were significantly elevated over control levels in all 3 patient groups, and sCD8 was mildly elevated. These results indicate enhanced immune activation which may be a common feature in the onset and/or progression of these idiopathic illnesses.