Chronic alcohol abuse impairs alveolar macrophage immune function and renders patients susceptible to severe pneumonia and acute lung injury. Macrophage maturation and immune function require priming by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by the alveolar epithelium and signals to the macrophage via specific cell surface receptors. The GM-CSF receptor is composed of a binding subunit (GM-CSFRα) and a signaling subunit (GM-CSFRβ), which must be coordinately expressed and inserted into the cell surface membrane in order for the macrophage to respond to GM-CSF stimulation. However, the effects of alcohol abuse on GM-CSF-dependent priming of the alveolar macrophage have not been examined. Therefore, we hypothesized that chronic ethanol ingestion interferes with GM-CSF signaling to the alveolar macrophage. To test this hypothesis, we first compared GM-CSF expression in the alveolar epithelium of rats fed an isocaloric liquid diet containing either ethanol or maltin-dextrin (control diet) for 6 weeks. We then examined alveolar macrophage cellular expression as well as membrane localization of each GM-CSF receptor subunit. Chronic ethanol ingestion had no effect on GM-CSF gene expression in alveolar epithelial cells (by PCR) or protein levels in the alveolar lining fluid (by ELISA). In parallel, chronic ethanol ingestion had no effect on GM-CSFRα or GM-CSFRβ gene or protein expression (by PCR and Western blot analysis, respectively) within the alveolar macrophages. However, chronic ethanol ingestion significantly decreased macrophage cell surface expression of both the GM-CSFRα and GM-CSFRβ subunits by ˜ 50% (by flow cytometry). In contrast, macrophage cell surface expression of the interleukin-6 receptor was the same in control-fed and ethanol-fed rats, suggesting that the defect in GM-CSF receptor expression is relatively specific. We conclude that chronic ethanol ingestion decreases macrophage cell surface expression of the GM-CSF receptor. Although ethanol ingestion has no effect on the expression of GM-CSF within the alveolar epithelium and does not inhibit cellular expression of the GM-CSF receptors in alveolar macrophages per se, it appears to interfere with trafficking and/or insertion of the GM-CSF receptor into the cell surface membrane. We speculate that GM-CSF treatment could improve alveolar macrophage immune function in critically ill patients with alcohol abuse and thereby decrease the morbidity and/or mortality associated with severe pneumonia or acute lung injury in these highly vulnerable patients.