In a placebo-controlled trial of a single preseasonal course of desensitization (immunotherapy) for ragweed hay fever, treatment with either crude ragweed pollen extract or purified pollen allergens showed a significant amelioration of symptoms. Immunologic studies employing the technique of pollen antigen-induced histamine release from isolated washed leukocytes of these patients showed that during treatment a decrease in cellular reactivity accompanied the apparent symptomatic improvement in some but not all of the patients. Titers of antibodies of the IgG class, which specifically block histamine release by pollen extract ("blocking" antibodies), were regularly raised by immunotherapy and were significantly higher in treated patients with mild symptoms than in those with severe symptoms. Reductions in cellular reactivity and rises in blocking antibody, however, did not fully account for the suppression of symptoms.