Specific unresponsiveness to BγG was demonstrated in thymectomized, irradiated Lewis rats restored with washed cells from intact lymphoid organs injected with soluble BγG and incubated for 2 hr in vitro. Both delayed sensitization and antibody formation against BγG were reduced in the recipient; responses to PPD and bovine γA-globulin were not affected. Unresponsiveness to soluble ovalbumin could be induced by use of the same technique. Evidence is presented that this phenomenon is not due to the transfer of either free antigen, with the production of low-zone tolerance, or of cell-associated (membrane-bound) antigen. Since comparable unresponsiveness was not induced by incubating lymphoid cells in suspension with BγG, it is suggested that a processing step may be necessary for the production of tolerance or, alternatively, that the physiologic environment of the lymphoid cells controls their reactivity with antigen.