Sterile tissues of human subjects free from infection and malignancy were assessed for an antigen that cross-reacts with the enterobacterial common antigen (ECA). Extracts of heated homogenates (HE) and ethanol-soluble (ES) fractions of liver, kidney, muscle, and heart tissues were examined for their capacities to react with ECA antibodies, as measured by hemagglutination procedures, and to elicit ECA humoral antibodies in rabbits. Both HE and ES extracts of human liver and kidney tissues specifically inhibited ECA hemagglutination. However, ES fractions of HE preparations demonstrated significantly greater inhibiton than their HE sources. In addition, both liver and kidney ES fractions primed rabbits for a rapid and specific secondary ECA humoral response to a single administration of ECA. The cross-reactivity noted between human tissue and ECA cannot be attributed to indigenous microorganisms present in the tissues, as subcultures of tissue homogenates were always sterile. Moreover, preliminary experiments with human fetal subjects, devoid of microbial flora, yielded similar results.