Youmans, Guy P. (Northwestern University Medical School, Chicago, Ill.), and Anne S. Youmans. Nonspecific factors in resistance of mice to experimental tuberculosis. J. Bacteriol. 90:1675-1681. 1965.-In contrast to viable attenuated mycobacterial cells, Escherichia coli lipopolysaccharide (LPS) did not produce an acute pulmonary granulomatous response in mice, did not decrease the tolerance of mice to early subsequent intravenous injections of viable attenuated mycobacterial cells, nor did it increase susceptibility to tuberculous infection when injected simultaneously with virulent mycobacterial cells. When the injection of E. coli LPS was followed by the intravenous injection of virulent mycobacterial cells, there was a moderate increase in resistance to tuberculous infection which was maximal 7 to 14 days after the LPS injection. The degree of increased resistance to tuberculous infection was approximately the same as that produced by nearly maximal tolerated doses of heat-killed attenuated mycobacterial cells, and to that produced by a trichloroacetic acid extract of heat-killed attenuated mycobacterial cells. It is suggested that the major, if not entire, immunizing component of heat-killed attenuated mycobacterial cells resides in a heat-stable "nonspecific" component. A "multiple response" theory of immunity to tuberculosis is proposed.