Exacerbation of prior pulmonary involvement may occur during neutropenia recovery. Granulocyte colony-stimulating factor (G-CSF)-related pulmonary toxicity has been documented in cancer patients, and experimental models suggest a role for G-CSF in acute lung injury during neutropenia recovery. We reviewed 20 cases of noncardiac acute respiratory failure during G-CSF-induced neutropenia recovery. Half the patients had received hematopoietic stem cell transplants. All patients experienced pulmonary infiltrates during neutropenia followed by respiratory status deterioration coinciding with neutropenia recovery. Neutropenia duration was 10 (4-22) days, and time between respiratory symptoms and the first day with more than 1000 leukocytes/mm3 was 1 (-0.5 to 2) day. Of the 20 patients, 16 received invasive or noninvasive mechanical ventilation, including 14 patients with acute respiratory distress syndrome (ARDS). Five patients died, with refractory ARDS. In patients with pulmonary infiltrates during neutropenia, G-CSF-induced neutropenia recovery carries a risk of respiratory status deterioration with acute lung injury or ARDS. Clinicians must maintain a high index of suspicion for this diagnosis, which requires eliminating another cause of acute respiratory failure, G-CSF discontinuation and ICU transfer for early supportive management including diagnostic confirmation and noninvasive mechanical ventilation.