Using a new animal model, the aims of this study were to assess the role played by purified lipopolysaccharide (LPS) and neutrophils in the pathogenesis of acute red-eye reactions (ARE) and corneal ulcers. In addition, IL-1αwas assessed for its implications in the formation of corneal ulcers. Following corneal abrasion, eyes of rabbits underwent single or double exposures to various doses of LPS fromPseudomonas aeruginosaorSerratia marcescens.This protocol induced ARE symptoms, and their severity depended on the dosage, number of LPS exposures, and type of LPS used (LPS fromS. marcescensshowing highest virulence). Corneal ulcers were induced by delivering a high dose ofSerratiaLPS (100 μg) followed by a low dose (10 μg). Histopathological examination revealed that both ARE and corneal ulceration were associated with prominent neutrophil infiltration. In addition, many lymphocytes and other monocytic cells infiltrated ulcerated ocular tissue. Tear fluids obtained from ulcerated eyes contained high concentrations of a protein recognized by anti-rabbit IL-1αantibodies as demonstrated by immunoblotting studies. The results indicate that LPS can induce ARE and corneal ulceration in the absence of any live bacteria. Moreover, the findings implicate the accumulation of neutrophils and IL-1α-related proteins in the pathogenesis of ARE and corneal ulcers.