A 7-year-old boy developed a severe hemolytic reaction following a bite by a spider. A hemorrhagic and necrotic lesion developed at the bite. Although the arachnid responsible was not available for identification, the syndrome is typical of bites by spiders of the genus Loxosceles and quite different from that associated with bites or stings of other arthropods of this geographic region. A specimen of Loxosceles reclusa was later collected in the patient's house. The mechanism of hemolysis and indeed the entire mode of action of Loxosceles venom is very little understood. Regarding a case they observed, Weiner and associates conclude, "It seems likely that the hemolytic system did not require participation of the patient's tissues in the production of antibodies." The Coombs test was negative in their patient but was positive in one case as reported by Nance. It was not done in the case reported here. Atkins et al. could not reproduce the massive hemolysis syndrome with Loxosceles venom in rabbits and guinea pigs, although intestinal and muscle hemorrhages were seen. The local necrotic lesions are readily produced in experimental animals. While reactions similar to the one reported here occur in only a small percentage of Loxoscles bites, they represent a potentially fatal complication. Therapy in this case was symptomatic and supportive except for administration of ACTH and prednisone before admission. These agents had no discernible effect on the course of the envenomation.