The parameters of nonspecific immunity (interferon, interleukin-1, tumor necrosis factor, and natural killers) changed in immune BALB/c mice after challenge with Machupo virus in doses of 1000 and 5000 PFU. After challenge with 1000 PFU the activity of the above parameters increased during the first three days and no cases of animal death occurred. After challenge with 5000 PFU the maximal values of interferon, interleukin-1, tumor necrosis factor, and natural killers were observed on days 5-7, the animals dying at the height of these values. Hence, the formation of specific humoral and cell-mediated immune response in BALB/c mice immunized with inactivated Machupo virus does not protect the animals from infection with the homologous virus in a dose of 5000 PFU. High mediator activity of nonspecific immunity factors on days 5-7 after infection augments the disease course and leads to earlier death of vaccinated animals in comparison with the same dose of the virus in nonimmune mice.