The specificity of the membrane immunofluorescence reaction obtained upon the exposure of viable Burkitt lymphoma biopsy cells to the sera of certain Burkitt lymphoma patients (Klein et al., 1966 a, b) was studied by testing representative negative and positive sera against Burkitt lymphoma cells and normal bone marrow cells from the same donor, as well as against a panel of allogeneic normal lymph node cells and chronic myeloid leukemia cells from Swedish patients, Sera giving highly positive reactions with Burkitt lymphoma cells failed to react or reacted only exceptionally with normal bone marrow cells of the same donors or the allogeneic non-Burkitt target cells. In contrast, an isoimmune serum from a multiply transfused donor gave highly positive reactions against both Burkitt and non-Burkitt target cells. Taken together with previous results, these findings speak against the involvement of blood group or transplantation antigens, leaving 2 main explanations: (a) a tumor-specific reaction, similar to the findings on virus-induced mouse lymphomas: (b) preferential nonspecific binding to Burkitt lymphoma cell surfaces of some globulin fraction appearing in the serum of Burkitt lymphoma patients after chemotherapeutically induced regression.