Venom from the brown recluse spider, Loxosceles reclusa, reacted with human erythrocytes to form venom-sensitized erythrocytes. These cells were agglutinated specifically by high dilutions of adsorbed rabbit antivenin or were lysed by normal blood group compatible human sera. The specific rabbit antivenin prevented venom from attaching to erythrocytes, from interacting with serum complement, and from producing dermonecrotic lesions in rabbits. Results of experiments involving heat inactivation and adsorption to erythrocytes provide circumstantial evidence to suggest that the three biological activities of venom could be associated with a single component or few components with similar properties. The component interacting with serum complement is immunologically distinct from a factor in cobra venom which possesses similar biological activities.