To study local lung inflammation, 34 subjects had endotoxin (1–4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]- α , TNF receptors [TNFR], interleukin [IL]-1 β , IL-1 receptor antagonist, IL-6, granulocyte–colony-stimulating factor [G-CSF], all p ⩽ 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1 α , MIP-1 β , all p ⩽ 0.001, but no change in growth-regulated peptide- α ). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p ⩽ 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR₁, TNFR₂, L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p ⩽ 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF- α increased by 8 h (all p ⩽ 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.