We examined the diagnostic value of acetaldehyde-hemoglobin adducts in the detection of heavy drinking and alcoholism. Acetaldehyde adducts from red cells were measured by new chromatographic and immunologic methods. The study population included 20 men with well-documented histories of chronic alcoholism, 18 men who were heavy drinkers, 22 male healthy control subjects, and 8 control subjects with liver disease that was not related to alcohol use. In addition, 20 healthy volunteers and 5 control subjects participated in the study to determine the effect of an acute dose of ethanol. The results that were obtained by the two new methods correlated significantly (r = 0.38, p = 0.002). With both methods, the concentrations of acetaldehyde-hemoglobin adducts were found to be significantly higher in red cells of heavy drinkers (p less than 0.001) and subjects with alcoholism (p less than 0.001) when compared with control subjects. Acetaldehyde-modified hemoglobins appear to have at least the same sensitivity (chromatographic determination = 50% and immunologic determination = 50%) to detect heavy drinking as the most widely accepted conventional biochemical markers of alcohol abuse, gamma-glutamyltransferase (39%) or mean corpuscular volume (17%). In a group of 20 healthy volunteers, acetaldehyde-hemoglobin adducts increased significantly even after a single high dose of ethanol (2 gm/kg), whereas there was no change in the conventional markers of alcohol consumption at the same time. Acetaldehyde-hemoglobin adducts assays should be useful for the detection of heavy drinking in clinical settings.