Pneumolysin, a cytolytic toxin from Streptococcus pneumoniae, has previously(1) been shown to interact in vitro with polymorphonuclear leukocytes in a variety of ways behaving as a chemotactic, lethal or lytic agent, depending on its concentration. In this study we examined the effect of leukopenia induced by administration of nitrogen mustard on the response of the rabbit to conjunctival instillation and intracorneal injection of pneumolysin. Control animals responded to instillation of crude and pure toxin with intense erythema and chemosis, and production of a thick discharge. No discharge and only traces of erythema and chemosis were noted in leukopenic animals. Leukopenic rabbits also showed a decreased capacity to respond to intracorneal injection of the toxin, particularly striking in the first 48 hours following pneumolysin injection, when opacification, discharge formation, chemosis, and erythema were found to be markedly less than in control animals. We conclude that the polymorphonuclear leukocyte plays a key role in the response of the rabbit eye to pneumococcal toxin. This system appears to be a good model for study of the inflammatory response to microbial products.