In 1965, we reported a "new" antigen, Australia antigen, in the serum of patients with leukemia.1Research since then has dealt with the epidemiology, genetics, and physical and chemical characteristics of the antigen,2Early in the investigation3it became clear that Australia antigen is closely associated with, or may itself be, a causal agent of viral hepatitis.26It is estimated that tens of millions of asymptomatic people carry the antigen chronically.1,2These deductions have resulted from a systematic study of antigens in human blood with use of sera from multiply transfused patients as sources of antibody. In 1961 Allison and Blumberg hypothesized that individuals receiving multiple transfusions would receive some serum proteins of a phenotype different from their own and would respond by producing antibodies. It was appreciated that both inherited and acquired antigens might occur in human serum and cause antibody formation in blood