Many virus infections in man and other species are accompanied by immunosuppression. This is clearly important in terms of the susceptibility of the host to secondary infections. The immunosuppression may also aid and abet the growth and persistence of viruses. An unresolved issue is the extent to which the extent of this immunosuppression is determined by the virulence of the infecting virus or resistance factors in the host, and particularly by factors that are genetically determined. The mechanisms of viral immunosuppression are indirect and direct. Indirect mechanisms such as interferon production and suppressor cells induced by infection undoubtedly contribute to viral immunosuppression in experimental models of virus infection. In man the direct inactivation of immunologically responsive lymphocytes seems to be the most important mechanism. Moreover, the persistence of viruses in human lymphocytes is being increasingly recognized.