Cytophilic macroglobulin was eluted (by heating at 56 C for 60 min) from lymphoid cells of mice immunized with subfractions of virulent Salmonella typhimurium SR-11 or vaccinated with an attenuated strain of S. typhimurium (RIA). No such macroglobulin was present on comparable cell populations from normal or adjuvant-injected mice. Cytophilic macroglobulin was also present in the sera of immunized mice. In mice immunized with RNA and protein-containing subfractions extracted from lysates of S. typhimurium SR-11, the cytophilic macroglobulin was present by 14 days after immunization, whereas it was present by 10 days in mice injected with living attenuated S. typhimurium RIA. This macroglobulin reacts specifically with protein-rich components present in the immunogenic subfractions of the whole bacterial cells and has been demonstrated to facilitate phagocytic uptake of virulent S. typhimurium SR-11. Moreover, a similar protein material was present in broth culture media in which the salmonellae were cultivated. Greater amounts were detectable in older (4 day) cultures.