Intrapleural insufflation of talc is an increasingly common method used to obtain pleurodesis. Successful pleurodesis is associated with the rapid onset of pleural fibroblast proliferation and the loss of delineating margins between the visceral and parietal pleura. The mechanism whereby talc achieves this effect is unknown. We hypothesized that talc causes pleural mesothelial cells to release a proinflammatory cytokine namely basic fibroblast growth factor which initiates and perpetuates the development of pleural fibrosis. Pleural fluid (PF) was obtained serially prior to and following talc insufflation at defined time points, from 15 patients undergoing talc pleurodesis via thoracoscopy. Biologic fibroblast growth factor activity in pleural fluids was measured using [3H]Tdr uptake. We found that following talc insufflation the ability of PF to stimulate fibroblast proliferation increased to 120% of control by 4 hours and 242% of baseline by 24 hours. Pleural fluid bFGF levels were measured by ELISA. bFGF levels increased following talc insufflation to 300% baseline and correlated with biologic growth factor activity. Addition of bFGF antibody decreased the biologic fibroblast growth of pleural fluids by 70-90%. There was an invense correlation between tumor size graded at thoracoscopy and bFGF level indicating that normal pleural mesothelium may be the primary tissue production bFGF. In vitro, human pleural mesothelial cells stimulated by talc demonstrated a dose and time dependent release of immunologically active bFGF. On transmission electron microscopy mesothelial cells were seen to actively phagocytose talc particles. We conclude that talc causes pleural mesothelial cells to produce biologically active bFGF in vivo and in vitro which plays a critical role in the development of pleurodesis.