Australia antigen [Au(l)] has many of the characteristics of an infectious agent and many of the characteristics of an inherited serum protein polymorphism. In multiply transfused patients with thalassemia there is an association between antibodies to genetic markers on immunoglobulins, a known serum protein polymorphism, and antibodies to Australia antigen. There is also evidence that Au itself is polymorphic. It is composed of five or more polypeptides which are immunologically similar to normal human serum proteins (IgG, albumin, transferrin, β-lipoprotein, and the β-la/lc-fraction of complement). Le Bouvier has demonstrated antigenic subtypes of Au; these appear to be inherited traits of the infectious agent. We are testing the hypothesis that the manner in which a particular individual responds to infection with Au is determined by an interaction of the host with the infectious agent and this in turn is largely determined by the genetic make-up of the host and the genetic composition of the agent.