Sixty-seven patients with a history of severe systemic reactions following honey bee stings were treated by immunotherapy (IT) with honey bee venom. During maintenance therapy all were submitted to a sting challenge under clinical conditions. 15 developed mostly minor symptoms of a systemic reaction while 52 showed only a local swelling at the sting site. Phospholipase A2-specific IgE, IgG and IgG subclass serum antibodies were estimated in samples obtained before IT and immediately before the challenge. Specific IgE decreased in reactors and in non-reactors. There was no difference between the two groups at any time. Specific total IgG, IgG1 and IgG4 increased in both reactors and non-reactors during IT. An early increase of specific IgG1, was observed while specific IgG4 remained elevated throughout the treatment. Specific total IgG was higher in reactors than non-reactors before the challenge, specific IgG1 higher in reactors before treatment and specific IgG4 higher in reactors than non-reactors both before treatment and before challenge. In the individual patient, no single antibody estimation or combination of various antibodies was predictive of the outcome of a sting challenge.