We measured the serum concentrations of the soluble form of interleukin-2 receptor alpha chain (sIL-2R alpha) in 25 patients with non-Hodgkin lymphoma (NHL) and 1 patient with virus-associated hemophagocytic syndrome (VHAS) by an enzyme-linked immunosorbent assay (ELISA) using two anti-IL-2R alpha monoclonal antibodies which recognize different epitopes. The sIL-2R alpha levels were markedly higher (n = 12, range = 469.2-11020 U/ml, mean +/- SD = 6153.0 +/- 1687.2 U/ml) in the sera of patients with NHL than in healthy individuals (n = 46, range = 290.1-849.3 U/ml, mean +/- SD = 459.8 +/- 126.9 U/ml, p < 0.01). The serum sIL-2R alpha levels in the NHL patients were closely associated with the stage of disease. The mean value of the serum sIL-2R alpha in each stage of NHL was as follows: stage I (469.2 U/ml, n = 1), stage II (4879.0 U/ml, n = 3), stage III (7364.8 U/ml, n = 8), stage IV (13796.2 U/ml, n = 10). However, there was no clear correlation between the elevation of serum sIL-2R alpha level and the pathological (LSG) classification of NHL. The serum sIL-2R alpha levels serially measured during the clinical course of 2 NHL patients were closely associated with the severity and the progression of the disease. Thus, the measurement of serum sIL-2R alpha levels is very useful not only for the diagnosis but also to monitor the clinical course of NHL.