Second-set reactions to skin graft in mice were used as the criterion in measuring the immunogenicity of liver and spleen tissue extracts and the inhibitory effect of the former. The different immunogenicity of extracts of the two tissues was shown to depend on immunogenetic donor-recipient differences; this is especially apparent when mixtures of both extracts are used. In strain combinations where liver extracts are incapable of sensitizing the host to a subsequent skin graft, the extracts can protect the host against the sensitizing activity of an immunogenic spleen extract administered simultaneously. The sensitizing activity of spleen extract can also be reduced by adding host-compatible extracts from fetal liver, spleen, or kidneys. These results seem to indicate some sort of competition between the antigens of various strength and the amount of the “ballast” nonantigenic components. We are inclined to conclude that the low immunogenicity of liver extracts results from: (1) the lower concentration of antigenic determinants and consequently a higher desensitizing capacity of the ballast components; (2) a difference in the antigens themselves; and (3) the possible presence of an antigenicity-neutralizing component specific for some tissues including liver.