Resistance and susceptibility to Listeria monocytogenes in mice was found to be related to (i) the innate ability of the nonimmune macrophages to kill or inhibit the growth of the organism during the first 24 to 48 h after infection; and (ii) the time of onset of acquired cell-mediated resistance. Resistant C57BI/6 mice were 10 times more efficient than susceptible BALB/c mice at suppressing the early growth of Listeria in the liver. Furthermore, the onset of acquired immunity occurred 24 to 48 h earlier in C57B1/6 than in BALB/c mice. Acquired immunity was measured by (i) fall in bacterial numbers in spleen and livers of infected mice, (ii) adoptive transfer of immunity to normal mice by using spleen cells from infected mice, (iii) delayed-type hypersensitivity skin testing, and (iv) uptake of tritiated thymidine by lymphocytes in the spleen.