Abstract.-Examples of inherited susceptibility to infection controlled by genes segregating at one or a small number of loci have been identified in lower animals. In this study we report data on what appears to be a similar situation in humans. "Australia antigen" is an antigen found in the sera of patients with acute and chronic hepatitis, and it may actually be a form of virus. It is very common in many tropical areas, and people in these areas having the antigen appear to be hepatitis carriers. The antigen is detected by immunodiffusion in agar gel (Ouchterlony method). Individuals with the antigen are designated Au(1) and those without it Au(0). Family studies involving 1797 different individuals residing on the island of Bougainville are consistent with the hypothesis that susceptibility to chronic infection with the "antigen" is controlled by an autosomal recessive gene (Au'). This confirms the conclusions previously arrived at from similar (but less extensive) studies on the island of Cebu. Individuals with this inherited susceptibility do not ordinarily have overt manifestations of hepatitis.The sign test was used to determine family clustering. Segregation analysis was performed by the method of C. A. B. Smith. In the 41 Au(0) X Au(0) matings, 53.8 recessives were expected in the offspring and 56 were seen (0.7 > p > 0.5). In the Au(1) X Au(0) matings, 40.1 recessives were expected and 42 were seen (0.7 > p > 0.5). The Au(0) X Au(0) matings were also analyzed by the method of Li and Mantel, in which the recessive ratio of 0.25 is expected by the genetic hypothesis. The values observed were 0.2527 for the Bougainville study and 0.2461 for the Cebu study.Inherited resistance and susceptibility to infection has been described in several animal species. There is a single gene-controlled factor which prevents infection of mice by a group of related viruses including yellow fever, West Nile fever, Japanese B encephalitis, and others but does not prevent infection with other viruses.1 Gowen2 has described inherited resistance to bacterial infection in mice and has emphasized the specific nature of the resistance which develops. There is evidence for inherited susceptibility to several forms of virus-induced neoplasms in animals. These include polyoma virus in mice,3 in which two or three independent genes may be involved in the determination of resistance;4 mammary tumor in mice;5 leukemia in mice, where the inherited factor appears to be related to the histocompatibility locus;6 Rous sarcoma;7 fowl leucoses;8 and others. In humans, several inherited diseases carry with them an increased susceptibility to infection; for example, patients with the 1108