Three dogs were treated for acute severe systemic reactions following Hymenoptera stings. The reactions were characterized clinically by CNS depression, shock, and hemorrhage, and clinicopathologically by inflammation, liver injury, renal disease, hypoproteinemia, and possible disseminated intravascular coagulation. The severe systemic reaction may have resulted from allergic mechanisms, toxic, nonimmunologic mechanisms, or both. Rapid correction of hypovolemia and prevention of vascular stasis are the most important aspects of treatment.