In order to evaluate the clinical significance of soluble interleukin-2 receptor (sIL-2R) levels in the serum of patients with Hodgkin's disease (HD), we tested the pretreatment sera of 82 patients. The HD patients had significantly higher sIL-2R levels than normal controls (4787 U/ml versus 290 U/ml; P less than 0.001). In patients presenting with B-symptoms, the median sIL-2R levels were significantly higher than in patients without B-symptoms (7978 versus 2128 U/ml; P less than 0.01). Patients in stage IVB had the highest sIL-2R levels (10,450 U/ml). Of 77 patients evaluable for response, all patients with sIL-2R levels less than 1000 U/ml achieved complete remission and no relapses occurred in this group after a median of 20 months. The fact that sIL-2R levels dropped after therapy, even in patients who suffered from progressive disease, suggests that Hodgkin and Reed-Sternberg cells are only a minor source of sIL-2R in HD. Therefore sIL-2R levels are of limited value as a marker of disease activity. However, pretreatment sIL-2R levels less than 1000 U/ml define a subgroup of adult HD patients with an excellent prognosis, and this fact might be helpful for the design of more custom-tailored therapy programs.