Background: Recent studies have demonstrated high levels of vascular endothelial growth factor (VEGF) in exudative pleural effusions and a possible etiologic role. The factors regulating VEGF accumulation in the pleural space are unknown. Transforming growth factor (TGF)-beta is a potent stimulator of VEGF expression in vitro. We hypothesized that TGF-beta induces VEGF production in pleural tissues, and, hence, the pleural fluid VEGF levels should correlate with the levels of TGF-beta in pleural fluid of different etiologies.Methods: Seventy pleural fluid samples were analyzed. These included 20 malignant, 13 post-coronary artery bypass grafting (CABG), 8 parapneumonic, 11 miscellaneous exudative, and 18 congestive heart failure (CHF) pleural effusions.Results: Pleural fluid VEGF levels showed good correlation with those of TGF-beta (1) (r = 0.58; p <0.0001), TGF-(2) (r = 0.43; p <0.001), and lactate dehydrogenase (r = 0.65; p <0.001). The levels of TGF-beta (1) and TGF-beta (2) also were correlated (r = 0.60; p <0.0001). The median levels of TGF-(1) (2,480 pg/mL) and TGF-beta (2) (266 pg/mL) in the CHF group were significantly lower than those in the malignant (TGF-beta (1), 4,902 pg/mL; TGF-beta (2), 428 pg/mL), post-CABG (TGF-beta (1), 5,456 pg/mL; TGF-beta (2), 377 pg/mL), parapneumonic (TGF-beta (1), 5,024 pg/mL; TGF-beta (2), 464 pg/mL), and miscellaneous exudate groups (TGF-beta (1), 7,690 pg/mL; TGF-beta (2), 369 pg/mL). There was no significant difference in TGF-beta (1) and TGF-beta (2) levels among the four exudate groups.Conclusions: VEGF levels in pleural effusions are significantly correlated with the levels of TGF-beta (1) and beta (2) isoforms. VEGF, TGF-beta (1), and TGF-beta (2) levels were all higher in exudative effusions than in effusions secondary to CHF.