Intravenous endotoxin produces an acute toxic ocular reaction in rabbits. The core component of endotoxin, lipid A, can be modified by acid hydrolysis. This results in a detoxified ST that is relatively ineffective in inducing fever or lethal effects but which retains activity as a mitosen or as a cofaotor in inducing tumor necrosis. We report that detoxified endotoxin was relatively ineffective in inducing iris hypereuia, increased ocular vascular permeability, a rise in aqueous humor prostaglandin E2, or the Ceneration of aqueous humor neutrophil chemotactic activity. Chemotaotic activity was not increased in aqueous humor even though detoxified endotoxin effectively generated chemotactic activity from serum in vitro. These observations indicate the critical role of lipid A structure in producing ET-induced ocular effects and show that the ability of ET to act as a mitogen, induce turaor necrosis, or generate serum chemotactic activity can be dissociated from its ocular toxicity.