Due to widespread availability, toxicity, and potential for use as a bioterrorism agent, ricin is classified as a category B select agent. While ricin can be internalized by a number of routes, inhalation is particularly problematic. The resulting damage leads to irreversible pulmonary edema and death. Our study describes a model system developed to investigate the effects of ricin on respiratory epithelium. Human bronchial epithelial (HBE) cells were cultured on collagen IV-coated inserts until polarized epithelial cell monolayers developed. Ricin was added to the apical or basal medium and damage to the cell monolayer was then assessed. Within a few hours after exposure, the cell monolayer was permeable to paracellular passage of the toxin. A mouse anti-ricin antibody neutralized ricin and prevented cellular damage as long as the antibody was present before the addition of toxin. These studies suggested that effective therapeutic agents or antibodies neutralizing ricin biological activity must be present at the apical surface of epithelial cells. The in vitro system developed here provides a method by which to screen potential therapeutics for protecting lung epithelial cells against ricin intoxication.