Summary. The CD95 system plays an important role in lymphocyte homeostasis, has been implicated in the development of lymphoid malignancies, exerts a tumour suppressor function, and contributes to drug-induced cytotoxicity. We hypothesized that mutations of CD95 may occur in childhood B-lineage acute lymphoblastic leukaemia (ALL), a disease known for its constitutive resistance towards CD95-mediated apoptosis. We investigated 32 primary Blineage ALL of childhood and five B-lineage ALL cell lines. All primary leukaemias expressed CD95 and bcl-2 to a variable degree. Most of the leukaemias were resistant towards CD95-mediated apoptosis. However, using SSCP analysis, no mutations in the coding and proximal promoter region could be detected. We conclude that the resistance towards CD95-mediated apoptosis observed in most de novo Blineage ALL is not caused by mutations of the CD95 death receptor.Keywords: CD95 (APO-1/Fas), apoptosis, B-lineage acute lymphoblastic leukaemia, mutation.The APO-1 (CD95/Fas) system is pivotal in maintaining both B-and T-cell equilibrium and plays an important role in growth control of other cell types (reviewed by Nagata, 1997). Many cell types, both normal and malignant, express CD95 including cells of B-lineage (Leithäuser et