The effect of Shiga toxins (Stxs) produced by Escherichia coli on human lung epithelial cells was investigated. Specific antibodies for Stxs positively stained lung tissue from a patient who died of hemolytic uremic syndrome associated with Stx-producing E. coli (STEC) infection, indicating the deposition of Stxs in the lung. Binding experiments with normal lung tissue revealed apparent Stx binding to both vascular endothelium and to portions of the pulmonary epithelium. CD77-positive lung carcinoma cell lines, which are derived from lung epithelium, showed binding to Stx and a high susceptibility to Stxs, as determined by MTT assay. Consistent with our previous reports on renal tubular epithelium, apoptosis is involved in the Stx-mediated cytotoxicity of these lines. These data indicate that lung epithelium is another target for Stxs, and Stx-mediated injury to lung epithelial cells is thought to play an important role in the pathogenesis of pulmonary involvement associated with STEC infection.