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Because of the rising importance of talcum pleurodesis in the therapeutic management of malignant and benign pleural effusions in Germany, pleural samples after talcum pleurodesis were compared to microscopic, immunohistochemical, and scanning electron microscopy findings after Tetracyclin and Novantron pleurodesis in 24 patients up to 18 months after intrapleural therapy. The histomorphological findings after talcum pleurodesis show an early phase of up to 4 weeks, characterized by the presence of talcum-containing granulation tissue with giant-cell foreign-body reaction, and a subsequent late phase with organization of the granulation tissue and connective tissue formation and obliteration of the pleura sheets. The resulting characteristic linear talcum zone in the pleural connective tissue is missing in cases with tumorous infiltration of the pleura. Continuous fibroblast activation, e.g., by macrophage or foreign-body giant-cell-released mediators, seems to be the decisive factor in the fibrosing process. No therapy-related tumor growth alterations could be demonstrated.