An enzyme immunoassay (EIA) for the detection and measurement of serum IgM, IgG, and IgA antibodies to salmonella was developed with commercially available lipopolysaccharides (LPSs) of Salmonella typhimurium and S enteritidis combined as antigen. Of 130 sera from patients with culture-confirmed salmonella infections, 115 (88.5%) were positive in this assay. The classic Widal agglutination test was positive in only 50 (38.5%) cases. This EIA method offers a substantial advance in the serological diagnosis of acute salmonella infections; it detects antibodies to the salmonellae of groups B and D, which constitute about 70% of culture-positive cases of human salmonellosis. Antibodies to other salmonellae are also detected. This EIA is particularly valuable for the detection of salmonella antibodies during post-infectious complications when isolation of the organism is often no longer possible.