The association of Australia antigen (AuAg) 2 with human type B hepatitis has been fully established. It has been reported that AuAg, which contains 6.5 M% of cysteine (1), completely lost the ability to react with humoral anti-Au antibodies after reduction and alkylation (2). Recently, Vyas et al. (3) have further reported that the reduced and alkylated AuAg could induce a delayed-type hypersensitivity response in guinea pigs but did not raise humoral antibody, suggesting the significance of the disulfide-bond dependent conformation in stimulating the humoral antibody response. We have found, however, that a part of the antigenic reactivity of AuAg was relatively resistant to reduction and alkylation, although most of it was sensitive to this procedure. This unexpected finding prompted us to study in detail the hitherto recognized antigenic determinants of AuAg—a, d, y, w and r3 —with respect to their susceptibility to the conformational changes induced by this chemical modification.