Several cytokines and the receptors for some cytokines are involved in the pathogenesis and progression of malignant lymphomas. CD95 (Fas/Apo-1) belongs to the TNF-receptor superfamily and may mediate apoptosis if triggered by Fas-ligand or specific antibodies. Recently soluble CD95 (a splice variant of the surface-bound molecule) was detected in the serum of patients with lymphoid leukemias and other disorders. In this study, we examined the levels of soluble CD95 (SCD95) in a series of patients with untreated malignant lymphomas and attempted to correlate this molecule with clinical, histological and laboratory parameters. The level of SCD95 was determined in the serum of 66 untreated patients with low and intermediate grade malignant lymphomas (NHLs) and in 20 normal controls using a solid phase ELISA. The total group of patients with NHLs had a trend towards increased values of SCD95 compared with normal controls (48.8+/-50.0 versus 75.0+/-136.3 U/ml, p < 0.1). However, among patients with NHL, elevated SCD95 did not correlate with the presence of B-symptoms, clinical stage, histologic subtype, LDH, beta-2 microglobulin, response to therapy or duration of response. We conclude that within the confines of this study, SCD95 has no prognostic value in patients with NHL.