Exposure of mice to aerosolized ovalbumin (OA) once weekly for 5 min, or once weekly to 10 microgram OA in PBS intranasally, elicited transient IgE responses which declined by the seventh week. When these animals were challenged intraperitoneally (i.p.) with soluble or alum-precipitated OA, their subsequent IgE responses were markedly suppressed relative to controls. In contrast, i.p. challenge provoked hemaagglutinating antibody (HA) responses to OA in the same animals which were considerably more vigorous than in controls. Adoptive transfer experiments employing splenocytes from mice repeatedly exposed to OA via the respiratory tract revealed the presence of suppressor cells active against OA-specific IgE but not HA responses. Radiotracer studies employing 125I-OA, administered intranasally and by aerosol, indicated that much of the antigen rapidly became associated with the gut.