Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL-2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell lines. In addition, soluble IL-2R alpha molecules were demonstrated in the supernatants of three of these cultured cell lines. In primary tissues, IL-2R alpha and IL-2R beta were seen in some but not all cases. Staining was detected in Hodgkin and Reed-Sternberg and in lymphoid cells. There was a remarkable difference in the pattern of expression, in that IL-2R alpha- but not IL-2R beta-positive cells from HD patients were clustered in frozen sections. We conclude from these data that IL-2R expression might be involved in the biology of HD.