Recent reports suggest that ethanol metabolism leads to reactive oxygen intermediates that may be responsible for the lesions observed in alcoholic hepatitis. This study investigated the production of reactive oxygen intermediates in peripheral blood phagocytes of patients with alcoholic hepatitis and attempts to evaluate its predictive value. Using a luminol-dependent chemiluminescence method, reactive oxygen intermediate production was measured directly within microamounts of whole blood, both in the absence (basal chemiluminescence production) and in the presence of phagocyte-stimulating agents including latex, zymosan, phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine. Thirty patients with well-documented and histologically proven alcoholic hepatitis were studied. Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function were used to assess the prognosis of the liver disease. Patients were followed up monthly for 6 mo. Results were compared with those obtained in 17 patients with nonalcoholic liver disease and in 78 normal control subjects. Basal chemiluminescence production was significantly higher in patients with alcoholic hepatitis than in those with nonalcoholic liver disease and in normal subjects (p < 0.001). Chemiluminescence responses to latex, zymosan and phorbol myristate acetate were significantly lower in alcoholic hepatitis patients than in normal subjects (p < 0.001); however, when compared with nonalcoholic liver disease patients, these responses were significantly decreased only in the presence of zymosan (p < 0.05). Both basal chemiluminescence production (p < 0.001) and zymosan-induced chemiluminescence responses (p < 0.02) were closely related to alcoholic hepatitis prognosis indices (i.e.), Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function. Patients with severe alcoholic hepatitis and unfavorable outcome exhibited more pronounced chemiluminescence alterations than patients with mild alcoholic hepatitis or those with favorable outcome. Although not based on conventional liver function tests, whole blood chemiluminescence determination appears to be a sensitive and discriminating test in evaluating the severity and prognosis of alcoholic hepatitis. (HEPATOLOGY 1990;12:264–272).