ABSTRACT The histopathologic evidence of the presence of neutrophils within the liver parenchyma is a prominent feature of alcoholic hepatitis in both experimental animals and chronic human alcoholics. However, the precise mechanisms by which neutrophils infiltrate the liver and cause liver injury still remain to be fully elucidated. For neutrophils to infiltrate the liver, they have to undergo systemic activation (priming) by proinflammatory cytokines, chemokines, complement factors, and other biologically active molecules (e.g., platelet-activating factor). Neutrophils accumulated in the hepatic microvasculature (sinusoids and postsinusoidal venules) can extravasate (transmigrate) into the hepatic parenchyma if they receive appropriate signals from previously sensitized or distressed cells. Transmigration can be mediated by a chemokine gradient established toward the hepatic parenchyma and generally involves the interaction between adhesion molecules on neutrophils (beta(2) integrins) and on endothelial cells (intercellular adhesion molecules [ICAM-1]). Following transmigration, neutrophils adhere to sensitized hepatocytes through their beta(2) integrins and ICAM-1 expressed on hepatocytes and mediate killing of hepatocytes mostly by oxidant stress and proteases. These neutrophilic events during chronic alcohol ingestion, based mostly on experiments with rodent models, will be emphasized in this review.