Cytosol fractions of lymphocytes from LPS-responder mice (C3H/HeN) were prepared and injected into B lymphocytes of LPS-nonresponder mice (C3H/HeJ) by a microinjection technique utilizing polyethyleneglycol-mediated cell fusion. The B lymphocytes of C3H/HeJ mice microinjected with cytosol prepared from LPS-stimulated C3H/HeN cells became normally responsive to LPS. Microinjection of cytosol itself did not stimulate C3H/HeJ cells to proliferate or differentiate into immunoglobulin-producing cells, and the cells injected with cytosol had to be restimulated with LPS in order to proliferate and differentiate. These data suggested that C3H/HeJ B cells acquired LPS responsiveness by microinjection of cytoplasmic factor(s) from LPS-stimulated C3H/HeN cells and that these factor(s) may be one of the components involved in normal signal transmission from cell surface to nucleus in the early stages of the LPS response. The apparent m.w. of the cytoplasmic factor(s) is 100,000 by gel filtration. Chromatofocusing analysis suggested that these factors may consist of two components with the same m.w.