To determine the efficacy of doxycycline as a pleural sclerosing agent, we examined the outcomes in 31 patients (aged 31 to 87 years) receiving doxycycline (500 to 1,000 mg) through a chest tube for malignant pleural effusions or persistent bronchopleural fistulae. Of the 27 patients with malignant pleural effusions, 21 patients had a complete short-term response (no fluid reaccumulation during the initial hospitalization); 5 of the 6 short-term nonresponders had partial control of effusions, with improvement in respiratory symptoms. Of the 23 patients who survived longer than 1 month, 15 patients did not have reaccumulation of fluid during follow-up. All four patients with persistent bronchopleural fistulae had resolution of their air leaks; one patient had recurrence with a partial pneumothorax. Pleural pain controllable with narcotic therapy was the only important complication. Thus, doxycycline is a suitable substitute for tetracycline as a pleural sclerosing agent.