Pleurodesis with doxycycline (100 mg and 600 mg) and Corynebacterium parvum (1 mg and 7 mg) were compared in 41 patients with malignant effusion. To evaluate the mechanisms, pleural fluid pH, leukocytes, granulocytes, interleukin-6 (IL-6) and serum IL-6, as well as C-reactive protein (CRP) were measured before and on 2 consecutive days after treatment. Corynebacterium parvum produced a greater acute-phase response measured with fever, serum CRP and IL-6 than doxycycline. However, no change in pleural fluid IL-6 was demonstrated. Among the 35 assessed patients, 26 had objective response, similar in all four treatment groups. Side-effects were more common with Corynebacterium parvum. Based on this preliminary study we conclude that doxycycline, even in low doses, is a highly effective and well tolerated agent for palliative treatment of malignant pleural effusion. As the responses were similar despite different inflammatory reactions, the two agents probably induce pleural obliteration through different mechanisms.