A wide variety of immune parameters may be influenced in vivo and in vitro during virus infections. Some viruses appear to specifically alter macrophage activity, while other viruses preferentially affect activity of lymphocytes, both B and T cells. There are many mechanisms involved in immune derangement during virus infection, including the possibility that viruses preferentially interact with selected classes of immunocompetent cells. Alternately, some of the events associated with viral derangement of the immune response may be associated with the release or formation of factors by cells infected with a virus which affects other cells of the immune system. Similarly, the development of immune complexes resulting from the interaction of viruses or their components with antibody directed to the virus may influence the immune response, as well as induce other immunopathologic manifestations. Many model systems have been studied, especially those with viruses important to human infection. It is noteworthy that leukemia viruses and, in some cases, other tumor associated viruses may directly alter the immune response, usually before other manifestations of the tumorigenic process is evident. Tumor virus-induced immunomodulation is associated with direct effects of a virus on immunocompetent cells per se as well as the formation of soluble factors induced by the virus infection. These and other considerations indicate that interactions of viruses with the host immune defense system are an important consideration in understanding how virus infection is initiated and progresses, and how such infection affects the host's physiologic activity, including immunocompetence, per se.