When spleen cells from mice infected with Rowson-Parr virus (RPV) were cultivated with sheep red blood cells (SRBC), antibody plaque responses were markedly lower than those in similarly cultivated spleen cells from normal mice. Addition of as few as 10(3) spleen cells from RPV-infected mice to cultures of normal aplenocytes markedly depressed the expected immune response. Although RPV-infected mice showed maximum immunodpression in vivo only during the first week after infection, their spleen cells, obtained later in the course of infection, depressed the immunologic responsiveness of normal splenocytes in vitro. Increased doses of SRBC or addition of bacterial lipopolysaccharide to cultures of spleen cells from immunodepressed, RPV-infected mice stimulated antibody formation, and near-normal numbers of antibody-producing cells were evident. Peritoneal exudate (PE) cells, but not thymus, bone marrow, or unfractioned spleen cells, restored immunocompetence to cultures of spleen cells from RPV-infected mice but did not affect the suppressive properties of the infected cells on normal splenocytes. The function of PE cell macrophages in restoring immunocompetence to infected spleen cells in cultures seemed related to a possible antigen-focusing activity of the cells; antibody-producing cell precursors in infected cultures seemed to be preferentially affected by the presence of normal PE cells.