BACKGROUND: Malignant pleural effusions are a common problem for patients with metastatic disease. Most patients are treated with tube thoracostomy and sclerotherapy, although there remains no standard approach. The purpose of this study was to compare the efficacy of bleomycin with doxycycline sclerotherapy for the treatment of malignant pleural effusions using small-bore catheters. METHODS: All patients with a symptomatic malignant pleural effusion referred for chest tube drainage and sclerotherapy over a 2-year period were considered eligible. Using image guidance, a 14F self-retaining catheter was inserted into the pleural space and connected to continuous wall suction. When drainage fell below 200 mL/d, patients were randomized to 60 U of bleomycin or 500 mg of doxycycline sclerotherapy. Response at 30 days was determined. RESULTS: One hundred six patients were enrolled in the study. Fifteen men (29%) and 37 women (71%) with a mean age of 57 years received bleomycin sclerotherapy. Twenty-one of the 29 patients (72%) alive and evaluable at 30 days had successful sclerotherapy. Twenty-three men (43%) and 31 women (57%) with a mean age of 61 years received doxycycline sclerotherapy. Twenty-three of the 29 patients (79%) alive and evaluable at 30 days had successful sclerotherapy. There was no significant difference in response rates between doxycycline and bleomycin (p=0.760). CONCLUSIONS: These data continue to support a role for small-bore chest drainage and sclerotherapy, although there was no significant difference in 30-day response rates between doxycycline and bleomycin.