The effects of local versus systemic treatment with soluble IL-4 receptors (sIL-4R) were tested in a model of allergen-induced immediate hypersensitivity responses in BALB/c mice. Mice sensitized through the airways to ovalbumin (OVA) by ultrasonic nebulization once a week for 4 weeks developed increased serum anti-OVA IgE and IgG1 antibody titers and these were accompanied by immediate-type skin test responses to the allergen. These responses were also associated with the development of increased airway responsiveness (AR) as monitored by electrical field stimulation of tracheal smooth muscle preparations in vitro. Sensitized mice, treated by intraperitoneal injections of sIL-4R (150 micrograms/injection) administered in parallel to the sensitization protocol, developed significant suppression of anti-OVA IgE, anti-OVA IgG1 antibody production and of immediate cutaneous hypersensitivity responses. Airway responsiveness was normalized to some extent. Total IgE production was only slightly reduced. These effects were comparable to the findings following intraperitoneal injection of monoclonal anti-IL-4 antibody. Administration of sIL-4R via the airways was also effective in inhibiting the development of immediate hypersensitivity responses, including IgE production, and was more potent in normalizing airway responsiveness. These effects were achieved at lower concentrations than needed for systemic treatment. These data suggest that delivery of sIL-4R via the airways can effectively modulate the development of immediate hypersensitivity and airway hyperresponsiveness in response to aerosolized allergen.