The effects on the immune response of daily feeding of 30 mg of human serum albumin to rats have been studied. Feeding for periods of 17–20 days consistently resulted in a specific systemic hyporesponsiveness evident on subsequent parenteral immunogen challenge. Local secretory sites such as the major salivary glands were not made hyporesponsive as evidenced by the salivary antibody titres and the enumeration of glandular plaque-forming cells. The levels and classes of antibodies present in the secretions and sera were identified by passive haemagglutination, and a sensitive red-cell-linked antigen-anti-globulin reaction. By the use of radioimmunoassay and haemagglutination inhibition assays it was possible to quantitate the amount of antigen appearing in the circulation at varying times after feeding. It was shown in the use of oesophagectomised rats that absorption of small amounts of intact protein occurs from undefined sites in the oral cavity. Attempts were made to transfer the specific systemic hyporesponsiveness to syngeneic animals using spleen cell and serum transfers.