Histologic specimens from 41 rabbits were studied for changes resulting from the manual injection of brown recluse spider venom. Major findings included a mixed inflammatory cell infiltrate, coagulative tissue necrosis, and vasculitis. All specimens demonstrated a well-delineated zone of eosinophilic staining recognizable as "mummified" coagulative necrosis of the epidermis and dermis. A dense band of neutrophils bordered the zone of necrosis. Immediately adjacent to the neutrophilic band, small vessel vasculitis was a universal finding. Degranulated eosinophils and neutrophils and macrophages filled with eosinophilic granules were common. Inflammatory foci were often centered on groups of lipocytes within the dermis. Large vessel vasculitis resembling that seen in polyarteritis nodosa was present deep to 7 of the 40 eschars. Large vessel vasculitis may contribute to the large zones of necrosis seen after some brown recluse spider bites. Eosinophils may play a role in tissue damage after envenomation.