Saliva antibodies to Escherichia coli O157 were investigated as markers of the immune response in children with enteropathic hemolytic uremic syndrome (HUS). Paired serum and saliva samples were collected from 22 children with HUS during acute disease and convalescence and were tested for E. coli O157 lipopolysaccharide (LPS)-specific IgM and IgA antibodies by ELISA. Serum and saliva samples from 44 age-matched controls were used to establish the cut-off values. Elevated levels of IgM and/or IgA antibodies to O157 LPS were detected in saliva of 13/13 HUS patients with Shiga toxin-producing E. coli (STEC) O157 in stool culture and from 4 of 5 HUS patients in whom STEC were not detected. These results closely mirrored the results obtained with paired serum samples. In contrast, saliva and serum samples from four children with STEC isolates belonging to O-groups O26, O145 (n ϭ 2), and O165 lacked detectable O157 LPS-specific antibodies. The specificity of the ELISA was confirmed by western blotting. In STEC O157 culture-confirmed cases, the sensitivity of the ELISA was 92% for saliva IgM and IgA, based on the first available sample, and 100% and 92%, respectively, when subsequent samples were included. The specificity was 98% for IgM and 100% for IgA. Children with E. coli O157 HUS demonstrate a brisk, easily detectable immune response as reflected by the presence of specific antibodies in their saliva. Saliva-based immunoassays offer a reliable, noninvasive method for the diagnosis of E. coli O157 infection in patients with enteropathic HUS. The clinical spectrum of STEC, especially of prototypic E. coli O157 strains, includes mild diarrhea, hemorrhagic colitis, and the classical (enteropathic) HUS (E ϩ HUS) (1-3). E ϩ HUS occurs predominantly in young children and in the elderly possibly because of a lack of immunity in these age groups (3, 4). It is characterized by a prodrome of gastroenteritis, frequently with bloody diarrhea, followed by acute microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Occasionally, other organs are also affected (4, 5). E ϩ HUS accounts for approximately 50% of acute renal failure in young children (4, 6). Outbreaks and sporadic infections by E. coli O157 have been reported from all inhabited continents (6). The largest recorded outbreak of E. coli O157 to date occurred in Sakai City (Japan) in 1996. It led to 12,680 cases of diarrhea and 121 of HUS and dramatically illustrated the pathogenic potential and public health importance of this organism (7). It also demonstrated the continuing need for simple and rapid diagnostic techniques.The detection of IgM and IgA, and IgG antibodies to STEC LPS O157, but also to non-O157 LPS in serum samples, has emerged as a useful and reliable diagnostic method (8 -13), especially when the bacterial isolation fails (13, 14). Two preliminary reports proposed the measurement of saliva anti-