Previous observations have indicated that acetaldehyde can bind irreversibly to proteins in vitro, yielding immunogenic determinants, which can stimulate production of antibodies against the acetaldehyde adducts. We have developed sensitive two-site enzyme-linked immunosorbent assays for measurement of hemoglobin-acetaldehyde adducts. These adducts were measured from the red blood cells of 169 alcohol abusers, 66 social drinkers, 18 abstainers, and 73 hospitalized control patients. While the immunoreactive acetaldehyde adducts were found to be increased in 50% of the alcohol abusers (p less than 0.01), 24% of the social drinkers (p less than 0.05) also exceeded the reference interval obtained from the abstaining controls. Adducts were also increased in 17 (23%) hospitalized controls, seven of whom could retrospectively be verified as heavy drinkers. Upon abstinence from ethanol, the adducts decreased during a period of 1-3 weeks. The studies indicate that acetaldehyde adducts are frequently elevated in the erythrocytes of human alcohol consumers. Measurements of such adducts may prove to be valuable in the early identification of excessive alcohol consumption and of hazardous social drinking and in the comprehensive assessment and treatment of patients with alcohol-related diseases.