Abstract： Objective　To determine whether the intrapleural injection of TNFα neutralizing Fab antibody fragment (anti-TNFα Fab) would prevent the pleurodesis that occurs after the intrapleural injection of talc or doxycycline. Methods　In a randomized blinded placebo controlled study, 34 New Zealand white rabbits were given 400 mg/kg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant via a chest tube. Half of the rabbits in each group were also given polyclonal affinity purified anti-TNFα Fab 2 000 units or saline as placebo immediately before and 12 hours after the injection of the sclerosants. Chest tube were aspirated at 12 hours intervals until their removal at 4 days. Rabbits were sacrificed at 28 days. The pleural fluid volume, cell counts, LDH and pleurodesis scores were compared among groups. Results　Both talc and doxycycline produced an exudative pleural effusion. The pleural fluid volume and LDH levels were significantly greater in the doxycycline group than talc group. However, the pleural fluid leukocyte counts in talc group were higher than doxycycline group. The administration of anti-TNFα Fab had no significant effect on pleural fluid volume, LDH or leukocyte counts in either groups. However, the intrapleural administration of anti-TNFα Fab results in a significant decrease in the pleurodesis score for the talc group than doxycycline group (1.8±0.9 vs 3.2±0.8). In contrast the pleurodesis score was virtually identical in the doxycycline group with (3.5±0.5) and without (3.4±0.7) anti-TNFα Fab. Conclusion　The intrapleural administration of anti-TNFα Fab diminishes the pleurodesis induced by talc but not that which results from doxycycline. These findings suggest that different mechanisms are involed with the two different sclerosants.