Influenza is the last great uncontrolled plague of mankind. Pandemics and epidemics occur at regular time intervals. The influenza viruses are divided into the types A, B and C and show unique variability of their surface antigens (hemagglutinin and neuraminidase). Influenza viruses of type A show the largest degree of antigenic variation which, in turn, resulted in the definition of a number of subtypes, each comprising many strains. By comparison, influenza viruses of types B and C exhibit much less variation of their surface antigens. As a consequence, no subtypes but many different strains have been recognized. The degree of antigenic variation correlates with the epidemiologic significance of the virus types, type A being the most and type C the least important. Two different kinds of antigenic variation have been recognized: In the case of minor variation of one or both surface antigens, the term "antigenic drift" is employed. Antigenic drift occurs with all three types of virus, it is caused by point mutations which increase the chance of survival of mutants in the diseased host. In addition, influenza A viruses show sudden and complete changes of their surface antigens in regular time intervals, resulting in the appearance of new subtypes. This event is called "antigenic shift". The mechanisms responsible for antigenic shift are poorly understood, only. In addition to the recycling of preceding subtypes, reassortment resulting from double infection of cells with strains of human and animal origin are considered possible explanations. By use of modern DNA recombinant technology, the base sequences of a series of virus genes and, as a consequence, the amino acid sequence of the corresponding antigens have been determined. By means of monoclonal antibodies, the antigenic structure of many influenza antigens has been further elucidated. It can be expected that further research on the molecular basis of antigenic variation could finally result in an understanding of the causal mechanisms. It is an outstanding feature of the epidemiology of influenza A viruses that a family of related strains prevails for a certain period of time and disappears abruptly as a new subtype emerges.(ABSTRACT TRUNCATED AT 400 WORDS)