The purpose of the present study was to determine whether the intrapleural injection of transforming growth factor β₂ (TGF- β₂) would produce a pleurodesis in rabbits. Single intrapleural injections of TGF- β₂ at doses of 5.00 μ g (n = 12), 1.67 μ g (n = 10), 0.50 μ g (n = 10), or 0.167 μ g (n = 4), or of the parenteral buffer alone (n = 5) were given in a volume of 2 ml to New Zealand white rabbits. Chest tubes were left in place for at least 72 h. Pleural fluid was aspirated at 24-h intervals and was measured and subjected to chemical analysis. The animals were killed 14 d after the injection. The intrapleural injection of TGF- β₂ resulted in a dose-dependent pleurodesis (on a scale of 0 to 4, where 0 = no pleurodesis and 4 = complete pleurodesis) with mean scores of 3.6, 2.6, 1.5, 0.7, and 0.3 for the groups that received 5.0, 1.67, 0.50, and 0.167 μ g of TGF- β₂ and buffer alone, respectively. Intrapleural injection of the larger doses of TGF- β₂ resulted in the formation of a large amount of pleural fluid. The fluid had a significantly lower white blood cell (WBC) count and lactate dehydrogenase (LDH) level than did the fluid that results from the intrapleural injection of 10 mg/kg doxycycline or 400 mg/kg talc slurry. On the basis of this study we conclude that a single intrapleural injection of TGF- β₂ induces pleurodesis in a dose-dependent manner. A dose of 5.0 μ g produced satisfactory pleurodesis in almost all of the rabbits so treated. Larger doses of TGF- β₂ induced larger pleural effusions with relatively low pleural fluid WBC counts and LDH levels. The ability of TGF- β to produce a pleurodesis in patients with recurrent pleural effusions or pneumothorax should be investigated. A single intrapleural injection of TGF- β₂ may produce a pleurodesis both safely and painlessly.