Diffuse pleural inflammation and fibrin deposition following the instillation of the sclerosing agent is considered necessary for a successful pleural symphysis. We hypothesized that an impairment in fibrin formation or an increased endopleural fibrinolysis would lead to failure of pleurodesis. To investigate changes in the pleural coagulation/fibrinolysis balance, we studied 75 consecutive patients who underwent thoracoscopy. Fifty-four of these patients with malignant pleural effusions and four with a benign recurrent effusion underwent thoracoscopic talc pleurodesis. Another four patients with malignancy and 13 with benign effusions had no talc poudrage performed and were included as a control group. Serial determinations of thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor (PAI), and D-dimer were made in pleural fluid samples taken at the beginning of thoracoscopy (baseline), immediately after thoracoscopic biopsies had been done (postbiopsy), 3 h after thoracoscopy--either with talc poudrage or without--and 24 and 48 h after the procedure, as well as in cases of recurrence of effusions (farline). Successful pleurodesis was obtained in 42 of 52 patients who could be evaluated (81%), and failure was seen in 10. Strong activation of coagulation and production of PAI was observed in all groups, including the control (no talc) group. Fibrinolytic activity (as expressed by D-dimer levels) showed a clear decline 24 h after talc poudrage in patients with a good outcome of pleurodesis, as oppossed to those with bad results and to the control group, and returned to the baseline by 15 d. We conclude that increased pleural fibrinolytic activity is associated with failure of pleurodesis, despite significant inhibitory activity of PAI in all groups.