The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating and chemotactic cytokines. In this study, we assessed the effect of alcohol ingestion on the expression of tumor necrosis factor-alpha (TNF-alpha), and the chemokines macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) from murine alveolar macrophages (AMs) cultured ex vivo. Two-week ethanol feeding resulted in substantial impairment in the lipopolysaccharide (LPS)-induced expression of TNF-alpha, MIP-2, and MIP-1 alpha mRNA, and protein from LPS-stimulated AMs, compared with cytokine production from AMs obtained from CD-1 mice receiving an isocaloric control diet. These findings indicate that ethanol feeding results in diminished production of chemotactic and/or activating cytokines from AMs ex vivo that may contribute to the impairment in lung inflammatory responses and antimicrobial host defense that is observed in the setting of alcohol ingestion/intoxication clinically and experimentally.