Repeated exposure of rats to an aerosol of ovalbumin (OVA) induced tolerance to subsequent parenteral challenge with the same antigen. In the low-IgE responder WAG strain, responses in both the IgE and IgG classes were affected, whereas rats of the moderate (Lou/M) and high-IgE responder BN strain developed high titers of anti-OVA IgG in serum during exposure with concomitant tolerance in the IgE class. Repeated parenteral challenge, however, failed to elicit significant secondary anti-OVA IgG responses in the Lou/M and BN strains, suggesting that the isotype specificity of induced tolerance in these strains was not absolute. Spleen and respiratory tract lymph node cells, but not serum from aerosol-exposed BN rats, were capable of transferring IgE isotype- and antigen-specific tolerance. Dose response experiments demonstrated that the low-IgE responder WAG strain was exquisitely sensitive to tolerance induction in response to antigen inhalation, being susceptible to dosages in the nanogram range; at least 1000 times more antigen was required in the high-IgE responder BN to induce comparable tolerance in the IgE class. It was also apparent that the IgE isotype was more readily suppressed than the IgG isotype in both high- and low-IgE responder strains.