The work of the author and others on the pathogenesis of lymphocytic choriomeningitis (LCM) virus infection is reviewed in order to explain a general concept of the way in which many viruses cause disease. This concept states briefly that many otherwise harmless viruses are suppressed, not by simple antibody response, but by rejection of the virus-infected tissue by the host. This reaction is essentially the same process as rejection of a graft or transplanted organ. Therefore, when the viral infection involves key organs or tissues, the host may kill itself in its attempt to reject the infected tissue. When the rejection (cellular immunity) is prevented by drugs or antilymphocyte serum, LCM disease is also prevented, since the virus itself is almost entirely harmless. This virus-infected tissue rejection mechanism depends upon the fact that the virus induces the formation of a new antigen in the surface of infected cells. Because of this, the host recognizes the infected cell as foreign and attacks it. When the infection (LCM) occurs in the newborn, or before birth, the host mistakes the virus-induced antigen as “self” and fails to react to it. In this case lifelong persistent infection results, but since the virus is basically harmless, the mouse appears normal. This mechanism of tolerance induction by the virus is believed to hold for several other virus infections, possibly including serum hepatitis of man and to a lesser extent, rubella. Long-term study of persistently infected animals reveals that disease does sometimes occur. This is very slow, however, with incubation periods lasting as long as several years. The slow disease in the case of LCM appears to be due to an autoimmune mechanism; with other diseases it may be due to damage by the virus itself. Virus-induced change of the cell membrane, therefore, is seen as a fundamental disease process. Recent work in the author’s laboratory indicates that it may cause many types of chronic disease and many of the effects of senility. Conceivably, some components of old age (at least as an experimental hypothesis) can be regarded as the result of persistent viral infection of the whole population.