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Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate.Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated.Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-β and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-β at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis.Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.