BACKGROUND The involvements of interleukin-6 (IL-6) and fibrinogen in cancer development were elucidated independently, irrespective of IL-6 activity to induce fibrinogen. This study was undertaken to clarify the clinicopathological association of these molecules in lung cancer patients with malignant pleurisy. METHODS IL-6, fibrinogen and the related molecules in blood and pleural effusion of 38 patients were assayed at 3-day intervals. RESULTS IL-6 levels were elevated in sera of 27 cases (71.1%) and in all the effusions with mean values of 20.5 and 9970.5 pg/ml, respectively. Their correlation in 22 cases who were examined on the same day was statistically strong (r = 0.902, p < 0.0001). Occasional elevations of tumor necrosis factor-alpha were independent of IL-6 elevation. Levels of plasma fibrinogen, fibrin(ogen) degradation products (FDP) and C-reactive protein (CRP) were more frequently elevated in the IL-6-elevated cases than those without IL-6 elevation. In all pleural effusions, fibrinogen levels were significantly decreased to <150 mg/dl with large elevations of FDP level. Immunocytologically, IL-6 was detected in cancer cells in 16 cases of adenocarcinoma in addition to host pleural cells, but its cellular positivity was not reflected in the IL-6 level in each pleural effusion. CONCLUSION Compared with lung cancer patients without malignant pleurisy, IL-6, fibrinogen, FDP and CRP levels in patients with malignant pleurisy were increased more frequently in their peripheral blood. These were basically attributed to systemic leakage of IL-6 from the affected pleural cavity, in which plasma fibrinogen induced in response to serum IL-6 was exudated and degraded predominantly to FDP.