To evaluate the hypothesis that lymphocyte stimulation can modify the bronchoconstrictive response to inhalational challenge with an allergen, we administered interleukin-2 (IL-2), an important lymphokine in lymphocyte activation and proliferation, to actively sensitized rats. Brown Norway rats received either human recombinant IL-2 (n = 8) or its vehicle (n = 7) twice a day from the ninth to the fourteenth day after active sensitization to ovalbumin (OA) and were challenged with an aerosol of OA. Lung resistance (RL) during the early response increased to a maximum of 698 +/- 230% and 180 +/- 26% of baseline values in the animals receiving IL-2 and vehicle, respectively (p less than 0.025). The late response was threefold greater in IL-2-treated than in vehicle-treated animals (p = 0.01). IL-2 increased OA-specific IgG levels in the serum, but it did not significantly affect total or specific IgE levels. IL-2 caused an inflammatory infiltrate around the airways with significant increases in eosinophils, lymphocytes, and mast cells prior to antigen challenge. Our results indicate that stimulation of cell-mediated immunity can affect airway responsiveness to antigen.