Persistent virus infections either show steady and relentless progress-scrapie, visna, or maedi-or persistence with reactivation, as does varicella-zoster. In either case host defence mechanisms are unable to control the infection. To understand the underlying defects it is necessary to know what limits the progress of virus infections under normal conditions. Several factors contribute to host resistance against viruses, and it is becoming apparent that their relative importance varies from one virus infection to another. The main findings will be reviewed in this paper, together with available observations on immune responses to persistent viruses. The simplest way to achieve progressive infections is for the agent responsible to be non-immunogenic, and this, as far as we know, is true of scrapie and related agents. Speculations on why immune responses are ineffective in other persistent virus infections can be offered. Immunopathological reactions to virus infections are also attracting current interest. Since they contribute to the lesions observed in persistent virus infections, they are also briefly considered in this paper.