Murine multipotential hematopoietic stem cells (CFU-s) bear an antigen (SC-1) which is recognized by heterologous antisera to mouse brain. We have found that cloned Thy-1 negative variants of the T-cell lymphoma RL male 1 are sensitive to complement-mediated cytolysis by anti-brain serum and can absorb the anti-stem cell activity from the antiserum. We have isolated several subclones derived from a primary Thy-1 negative variant which are not susceptible to anti-brain serum. The surface of the resistant lines has little or no antigen capable of binding anti-mouse brain antibodies as measured by either immunofluorescence or a radioimmunoassay. These lines are also unable to absorb the antibodies responsible for the cytotoxic effect of rabbit anti-mouse brain serum against CFU-s. We conclude that the predominant antigen, serologically detectable on Thy-1 negative variants of RL male 1, is SC-1.