The pathomorphological patterns and the activity of serum interferon, interleukin-1, tumor necrosis factor, natural killers, and proliferative activity of lymphocytes were studied in BALB/c and C57B1/6 mice intracerebrally infected with Machupo virus. The BALB/c mice showed 100% lethality at 8-9 days after inoculation while C57B1/6 mice were found nonsusceptible to Machupo virus inoculation by this route. The pathomorphological findings at the peak of clinical manifestations in BALB/c mice revealed no organ whose functional deficiency could lead to the death of the animals. Investigations of nonspecific immunity parameters revealed a direct dependence between their high activity and susceptibility of the animals to Machupo virus infection. It is assumed that the endogenous shock due to the high activity of immune response mediators is the cause of death in Machupo virus infection.