Harvester ant stings by Pogonomyrmex maricopa (Pm) or Pogonomyrmex rugosus (Pr) resulted in serious reactions in 8 patients, 4 with generalized reactions and 1 with large local reactions. Exposure to one species in the genus Pogonomyrmex (P) appeared to cross-sensitize ant-sensitive patients to other species in the same genus as evidenced by skin testing and leukocyte histamine release, but these patients were less sensitive to extracts from other stinging Hymenoptera, including bee, wasp, yellow jacket, hornet, and Formica ant. Pr ant venom was obtained by electrical stimulation of live ants for leukocyte histamine release studies. The venom preparation was considerably more effective in inducing histamine release than a body extract derived from gasters, the posterior abdominal segments. Rabbits immunized with an extract from one species produced precipitating antibodies against the injected extract withich cross-reacted with extracts from other species of harvester ant, but not with other stinging Hymenoptera. Humans and rabbits appear to react to certain genus-specific antigens present in Pogonomyrmex whole body extracts. Proper identification of the offending ant is crucial for proper testing and treatment of ant-sensitive patients.