The central role of alveolar macrophages in the establishment of lipopolysaccharide (LPS)‐induced lung inflammation is well demonstrated. They produce and release numerous proinflammatory molecules, among which is tumor necrosis factor α (TNF‐α), a cytokine responsible in part for the neutrophilic alveolitis. Interleu‐kin‐10 (IL‐10) produced by LPS‐activated mononuclear phagocytes is a major anti‐inflammatory cytokine that down‐regulates TNF‐α synthesis. We studied the ability of murine alveolar macrophages to produce IL‐10 in vivo and in vitro, in response to LPS. Unexpectedly, the IL‐10 protein was not detected in the whole lung and airspaces after LPS intranasal instillation. In addition, no IL‐10 protein was found in supernatants of isolated and LPS‐stimulated alveolar macrophages. The lack of IL‐10 synthesis was confirmed by the absence of specific RNA transcripts. By contrast and as expected, autologous peritoneal macrophages produced IL‐10 upon LPS challenge. Drugs that usually modify the TNF‐α/IL‐10 balance in favor of IL‐10 were used without success. Thus, maneuvers allowing an increase in intracellular cAMP concentrations did not reverse this unexpected phenotype. Moreover, direct activation of protein kinase C with PMA was unable to trigger IL‐10 formation by alveolar, by contrast to peritoneal, macrophages. The current findings describe a specific phenotype for murine alveolar macrophages during LPS‐induced inflammation. J. Leukoc. Biol. 67: 545–552; 2000.