Recent studies have reported fever as a side effect of talc poudrage during thoracoscopic pleurodesis. However, thoracoscopy itself is likely to induce systemic inflammatory reaction, as it is an interventional procedure. The aim of the study was to investigate whether systemic inflammatory response is due to talc poudrage or to thoracoscopy.We prospectively studied two groups of patients. The first group (18 patients) underwent thoracoscopic talc poudrage, and the second group (17 patients) underwent only diagnostic thoracoscopy. We measured body temperature, as well as WBC count and C-reactive protein (CRP) levels before the procedure (baseline), and at 24 and 48 h after the procedure. No antiinflammatory medication was permitted to be used before, during, or after the procedure. All patients had a 3-month follow-up.The baseline patient characteristics were similar in both groups. Temperature increased significantly in the thoracoscopic talc poudrage group (overall comparison, p = 0.005) especially at 9, 12, and 24 h after the procedure. Overall, the WBC count (p = 0.004), percentage of neutrophils (p = 0.03), and CRP levels (p < 0.0001) were significantly increased in the group of patients who underwent thoracoscopic talc poudrage. On the contrary, lymphocytes were significantly decreased (overall comparison, p = 0.01) in the thoracoscopic talc poudrage group during the same period. Mild side effects, such as pain during and after thoracoscopy and subcutaneous emphysema, were noted. No severe complication, such as infection or acute respiratory failure, was noted in either group during the hospitalization or during the follow-up period.According to our results, fever and systemic inflammatory reaction is due to talc poudrage and not to thoracoscopy.