Acute respiratory failure revealing acute monocytic leukemia is rare. We report 20 patients admitted to the intensive care unit (ICU) with three remarkable features: (1) rapidly progressive respiratory distress revealing acute leukemia, (2) monocytic leukemia, and (3) respiratory status deterioration after chemotherapy initiation. The median age was 50 years (17-72 years), and respiratory symptoms started 2 days (0-15 days) before ICU admission. The median leukocyte count was 98,250/mm3 (800-529,000), with circulating monocytic cells in all of the patients but one. Bone marrow examination was diagnostic of monocytic leukemia in all patients. At presentation, respiratory rate was 33 (18-50) per minute, and PaO2 on room air was 44.5 mm Hg (30-60). Chest radiographs revealed unilateral alveolar infiltrates (n = 1), bilateral alveolar infiltrates with (n = 3) or without (n = 11) pleural effusion, or diffuse interstitial infiltrates (n = 5). Alveolar hemorrhage was the main bronchoalveolar lavage finding, with monocytic cells retrieved from four patients. Respiratory function deteriorated after cancer chemotherapy initiation in all patients. Of the 15 patients who required mechanical ventilation, 10 died. Leukemic pulmonary infiltration as the first manifestation of acute monocytic leukemia should be recognized, and intensive management should be provided in anticipation of the respiratory function deterioration seen consistently after chemotherapy initiation.