The purpose of this article is to review the nature of the immune response to influenza virus both in hosts which experience natural infection, particularly man, and in hosts which are experimentally infected, particularly mice. Until recently, an article on this topic may well have contained only a rather superficial account of the properties of the virion with hardly a mention of the replication process. However, the past few years have seen great advances in two almost separate developments. On the one hand, detailed information is now available on the viral genome and the expression of viral proteins: there are complete amino acid sequences and X-ray crystallographic analysis of the two surface glycoproteins, the hemagglutinin and the neuraminidase; we have a greater understanding of the roles of gene reassortment and mutation in the generation of antigenic shift and drift, and of the mechanism of viral replication and assembly. On the other hand, and although there are still very significant gaps, there has been a great increase in our knowledge of the different classes of lymphocytes, particularly T cells, and to a lesser extent of other cell types involved in the immune response to this virus. Significant correlations in the case of human studies and the findings from cell transfer studies in experimental systems have made possible the allocation of particular roles to different cell types. These two different approaches-the" virological" and the" immunological"-are now coming together. The neutralization of influenza virus by some classes of antibody may be explicable in terms of the viral replication cycle; evidence is beginning to accumulate that monoclonal antibodies which are very efficient in viral neutralization react with conformational (discontinuous) determinants of the hemagglutinin; linear amino acid sequences with secondary struc-