Objectives: To determine granulocyte colony-stimulating factor (G-CSF), epithelial neutrophilactivating peptide (ENA)-78, and interleukin (IL)-S in BAL fluid (BALF), epithelial lining fluid (ELF), and serum for establishing the concentration gradient of G-CSF, ENA-78, and IL-S between the blood and the alveolar space in ARDS and acute lung injury (ALI); and to evaluate the relationship of G-CSF, IL-8, and ENA-78 to pulmonary neutrophilia and severity of lung injury. Design: Prospective study. Setting: An adult trauma/surgical ICU. Patients: Nineteen patients with ARDS and 10 patients with ALI. Interventions: None. Measurements and main results: BAL and blood sampling simultaneously within 12 h and 24 h after onset of ARDS/ALI; G-CSF was detected in BALF in IS of 19 patients with ARDS, in 7 of 10 patients with ALI, and in all serum samples. G-CSF in BALF and serum was significantly higher in ARDS than in ALI. ENA-78 was detected in BALF in 14 of 19 patients with ARDS, in 8 of 10 patients with ALI, and in serum of all patients. Levels in BALF and serum were not different between ARDS and ALI. IL-S was detected in all patients; concentrations in BALF in ARDS were significantly higher than in ALI. Concentrations of G-CSF, ENA-78, and IL-8 in ELF were significantly higher than in serum. G-CSF in BALF and serum and IL-S in BALF correlated positively with pulmonary neutrophilia. G-CSF in serum and IL-S in BALF correlated negatively with Pao(2)/fraction of inspired oxygen (FIo(2)) ratio. However, ENA-78 did not show a correlation with neutrophil count or with PaO(2)/Fio(2) ratio. Conclusions: G-CSF may be pathophysiologically important for accumulation and activation of neutrophils in ARDS. Local G-CSF production is the likely driving force for neutrophils rather than elevation of circulating levels. In comparison to ENA-78, IL-S seems to be the predominant neutrophil chemoattractant in the early phase of ARDS.