Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-α (TNF-α), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-α expression may be induced in other cell populations before serious liver disease develops has not been evaluated. To clarify this issue, mRNAs and/or protein levels of TNF-α and cytokines [interleukin (IL)-6, IL-10, transforming growth factor-β(TGF)-β, IL-12, and interferon-γ] that regulate its biological activity were measured in sera, liver, and adipose tissues of rats that had developed hepatic steatosis after consuming ethanol-containing diets for 6 weeks. Cytokine expression in the ethanolfed groups was compared with that of pair-fed controls rats that had received isocaloric amounts of a similar, ethanol-free diet for the same time period. Animals were studied both before and after a surgical stress (partial hepatectomy) that is known to provoke cytokine production. Chronic ethanol consumption led to increased serum concentrations of TNF and related cytokines, at least in part, by inducing the overproduction of these factors in the liver and peripheral adipose tissues. Despite the pair-feeding protocol that ensured similar calorie consumption in both groups, adipose tissues in ethanol-fed rats also expressed more leptin, a TNF-α-inducible mRNA that encodes an appetite-suppressing hormone. Thus, white adipose tissue can be an important source of cytokines in nonobese animals and may be a target for ethanol's actions. These data implicate TNF-α as a potential mediator of the nutritional-metabolic ab-berratJons that often accompany chronic alcohol intake, even in the absence of advanced liver disease.