The two agents most commonly used for producing a pleurodesis are tetracycline and bleomycin. Tetracycline is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether bleomycin is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg, or bleomycin, 1.5 or 3.0 IU/kg diluted to a total volume of 1 ml with bacteriostatic saline solution. Twenty-eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of bleomycin was ineffective in creating pleural fibrosis, either grossly or microscopically. The mean degree of gross pleurodesis in the six rabbits who received tetracycline was 2.7 +/- 1.5 (scale 0 to 4), while that in the rabbits who received the highest dose of bleomycin was 0.0 +/- 0.0. Based on this study, we recommend that bleomycin not be used as a pleural sclerosant in patients with nonneoplastic pleural disease, eg, those with pneumothorax, congestive heart failure or cirrhosis, and pleural effusion.