We investigate the mechanism of talc pleurodesis (TP) in 20 patients with recurrent malignant pleural effusion and 10 patients with nonmalignant pleural effusions. We measured IL-8 levels before and 6h after TP and find a significant threefold increase (2.26ng/mL 0.7 to 6.5ng/mL 0.1), which explains the recruitment of inflammatory cells in these patients. We hypothesize that TP is enable by stimulating the mesothelial cells (MS) to secrete FGF. A significant tenfold increase in FGF-b (0.05ng/mL 0.02 to 0.44ng/mL 0.6) was seen 24h after talc instillation (P ≤ 0.04). In order to examine whether FGF-b is secreted by MS cells, MS recovered from CHF patients with recurrent pleural effusions were cultured for 48h in the presence or absence of increasing concentrations of talc (from 100ng/mL to 1mg/mL). They produced significant levels of FGF-b in a dose dependent manner (P ≤ 0.005). We hypothesized that a successful pleurodesis involves an early enhanced recruitment of inflammatory cells through a rise of IL-8 followed by enrollment of fibroblasts from the submesothelial space through increased mesothelial FGF-b production.