24 patients with honey bee sting allergy were treated with either honey bee venom (HBV) or monomethoxy polyethylene glycol-coupled HBV (PEG-HBV) in a double blind trial. Both treatments induced a strong increase in HBV-specific IgG antibodies in most patients. Immunotherapy with PEG-HBV was much better tolerated than that with HBV. Conversely, patients on HBV did considerably better during a sting challenge with a living honey bee. Only 4 developed a large local and one a mild systemic reaction compared to 7 large local and 3 moderate to severe systemic reactions in the PEG-HBV-group. A higher maintenance dose of PEG-HBV may still be well tolerated but prove more effective at reexposure.