After intrapleural instillation of talc for sclerosis of malignant pleural effusions, dyspnea occurred in three patients, progressed gradually over 72 hours, and culminated in acute respiratory failure characterized by bilateral diffuse pulmonary infiltrates with normal pulmonary artery occlusion pressures. Two patients recovered and one died. The chronological similarity of the sequence of fever, dyspnea, and respiratory failure in the absence of documented infection or other conditions that predispose to the adult respiratory distress syndrome (ARDS) suggests that intrapleural talc may have induced the syndrome in these patients through unknown mechanisms. This experience emphasizes that other agents are preferable for initial attempts to promote pleural symphysis in the palliation of recurrent malignant effusions. When talc is used in patients who are unresponsive to tetracycline, we suggest clinical monitoring for respiratory compromise for 72 hours after the procedure.