Mice of 7 inbred strains (A, A2G, BALB/c, CBA, C3H, C57BL/6, and DBA/2) were immunized with aequous liver extracts of the same strains. Each strain was split into 7 groups immunized with liver extracts of the different strains. Some combinations yielded precipitating antibody. Syngeneic liver extracts neither induced precipitating antibody nor could they boost a preexisting antibody level. CBA, C3H and DBA/2 liver extracts were capable of inducing a precipitating antibody in A and A2G whereas A, A2G, BALB/c and C57BL/6 liver extracts induced the same antibody in CBA and C3H. This antibody was called anti-F. The immunogenic determinant of the antigen was inherited like a dominant character, the capacity to form antibody against the F-antigen like a recessive character. Four types of strains were distinguished with respect to immunogeni-city and tolerogenicity . The existence of one genetic locus with 4 alleles governing the F-antigen was postulated. The F-antigen was organ specific and was present in the livers of all mammals tested so far (including man). As the F-antigen was also found in the antibody-producing animal, anti- F behaved like an autoantibody. Histological changes found in animals immunized with liver extracts and Freund adjuvant were similar to those found in the control groups which received Freund adjuvant only.