Honeybee and vespid venom-specific IgE were measured by RAST in randomly selected sera of 87 patients who had had anaphylactic reactions after insect stings. Overall there was a poor correlation between the titers of honeybee venom and yellow jacket or hornet venom-specific IgE. Sera from nine patients with high titers of both honeybee venom and yellow jacket venom-specific IgE were selected for RAST-inhibition studies, with these two venoms as coupling and inhibiting antigens. Three patterns of IgE-antibody specificity were detected. Four patients had unique antibody activity with no cross-reactivity between the yellow jacket and honeybee venom-specific IgE. This is probably the most common pattern in patients with dual sensitivity. Three patients reacted to a major allergen in yellow jacket venom cross-reacting with a minor allergen in honeybee venom. Their RAST-inhibition patterns demonstrated that the yellow jacket-venom RAST was inhibited by yellow jacket venom only and the honeybee-venom RAST was inhibited by both yellow jacket venom and honeybee venom. Two patients had the opposite pattern with honeybee-venom RAST inhibited by honeybee venom only and the yellow jacket RAST inhibited by both honeybee venom and yellow jacket venom. These latter patients reacted to a major allergen in honeybee venom that was cross-reacting with a minor allergen in yellow jacket venom. Studies with rabbit antisera raised to vespid and honeybee venoms demonstrated major antigens that were unique to each family that did not cross-react and several minor cross-reacting antigens.