Many strains of mice, when injected at birth with an ordinarily lethal dose of lymphocytic choriomeningitis virus (LCMV), grow to adulthood despite maintaining a persistent virus infection and chronic virus-induced immune complex disease. Because the susceptibility to LCMV infection changed over several years of observation, a number of murine strains with different histocompatibiity gene loci and genetic backgrounds were compared. Neonatal mice with H-2b, H-2d, and H-2q backgrounds were relatively insensitive to the effects of LCMV infection compared to mice with H-2k backgrounds, which had a high mortality rate in this situation. Expression of the H-2k gene locus itself did not affect the rate of mortality. Use of recombinant mice indicated that susceptibility was linked to H-2k backgrounds and not H-2k gene loci. The low survival rate of newborn mice with H-2k backgrounds infected with LCMV was not caused by cytotoxic natural killer cells, cytotoxic T lymhocytes, excessive amounts of virus in the organs, a unique distribution of virus or expression of viral antigens in vivo or unusual pathology in tissues.