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Background: Transforming growth factor (TGF)-β2 can produce effective pleurodesis in animals, but its efficacy has not been compared with commonly used pleurodesing agents in sheep, which have a thick pleura resembling that of humans. The acute physiological effects and the level of systemic TGF-β absorption after its intrapleural administration have not been studied. The aims of the present study were to compare: (i) the effectiveness of TGF-β2, talc and bleomycin in producing pleurodesis in sheep; (ii) the acute side-effects and systemic TGF-β levels following the intrapleural administration of these agents; and (iii) histological changes after intrapleural injections of these agents. Methodology: Twelve sheep were divided into three groups and were given a single intrapleural dose of TGF-β2 (0.25 μg/kg), talc slurry (5 g) or bleomycin (60 IU) via a chest tube. Saline or buffer was injected into the contralateral side, which served as the control. Arterial blood gases and respiratory and heart rates were monitored for the first 24 h. Plasma levels of TGF-β1 and TGF-β2 were measured. Pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50% of hemithorax) at day 14. Results: At day 14, the pleurodesis score of the TGF-β2 group (7.7 ± 0.6) was similar to that of the talc (7.0 ± 1.7) group and significantly higher than that of the bleomycin group (3.3 ± 2.3; P < 0.05). No significant differences were seen in arterial blood gas analysis, vital signs and plasma TGF-β1 and TGF-β2 concentrations among the three groups. Conclusions: Transforming growth factor-β2 was as effective as talc and more so than bleomycin in inducing pleurodesis in sheep. Intrapleural administration of TGF-β2 appeared safe. No acute changes in gaseous exchange or macroscopic abnormalities were seen following intrapleural TGF-β2. Importantly, there was no evidence of an increase in systemic... [ABSTRACT FROM AUTHOR]