To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine other had, in addition, a serum urea nitrogen level of over 100 mg per diciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P less than 0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia.