A model to study the dermonecrotic effects of a crude fraction of venom from the brown recluse spider (Loxosceles reclusa) was developed using female New Zealand white rabbits. In the rabbit model, surgical excision of the sites of intradermally injected crude venom did not always prevent subsequent necrosis or wound dehiscence despite the use of fluorescein to determine the surgical margin. Heparin and steroids did not prevent the venom-induced necrosis and were much less effective than surgical excision or injecting a specific antivenom. When given within 24 hours, the specific antivenom raised against the brown recluse spider venom blocked or markedly attenuated the toxic effects of the venom in the rabbit model system.