BACKGROUND: The standard treatment of recurrent, symptomatic malignant pleural effusion is intrapleural instillation of a chemical agent in an attempt to achieve a sterile inflammation and pleurodesis. There are many drugs used as pleural sclerosing agents, but the efficiency and side effects are different. The present study was undertaken to compare the commonly used drugs, doxycycline and bleomycin. METHODS: Thirty-four patients with malignant pleural effusion who needed repeated thoracentesis were randomized to receive treatment with--intrapleural instillation of doxycycline or bleomycin. Fluid volumes before and after pleurodesis, drainge time, and side effects were analyzed, and the response to treatment was evaluated by clinical examination and chest radiography during admission in the hospital. Also median survival time were evaluated according to the responses. RESULTS: The response rate was higher in the patients receiving doxycycline than in those receiving bleomycin (87.5% vs 50.0%, p=0.02), and fever, nausea and vomiting were more common in the patients receiving bleomycin. The median survival time was significantly longer in the patients who responded to the sclerotherapy regardless of sclerosing agents. CONCLUSIONS: Chemical pleurodesis with doxycycline or bleomycin could reduce or stop pleural effusions and prolong the median survival times in these patients. Doxycycline appeared to be more efficient as sclerosing agent than bleomycin in the short-term follow-up periods. But a prospective study with a larger number of patients is warranted.