It has been suggested that a proportion of patients with cancer have an ongoing acute phase response indicated by a raised C-reactive protein (CRP). To examine whether an acute phase protein response is associated with circulating interleukin-6 (IL-6) concentrations in patients with lung cancer, we measured serum levels of CRP and interleukin (IL)-6 in 176 patients with lung cancer and 48 patients with other pulmonary diseases (28 diffuse pulmonary infiltrates, 15 benign lung tumors, and 5 bronchial asthmas). Serum CRP was detectable (greater-than-or-equal-to 2.5 mg/liter) in 57.4% of patients with lung cancer, 78.6% of patients with diffuse pulmonary infiltrates, 46.7% of patients with benign lung tumors, and 40.0% of patients with bronchial asthma. Serum IL-6 was detectable in all patients by a highly sensitive enzyme-immunoassay, the concentration ranging from 0.126 to 35.115 pg/ml. Although there was no significant difference in serum IL-6 levels among the histologic types of lung cancer, the IL-6 concentration was significantly higher in patients with advanced cancers than in those with early ones. Correlation analyses showed that there was no significant relationship between the CRP and IL-6 concentrations in the 176 patients with lung cancer (r=0.212, P=0.1243), while a highly significant correlation between both levels was observed in the 28 patients with diffuse pulmonary infiltrates (r=0.783, P=0.0005). These results indicate that the serum IL-6 level in patients with lung cancer is closely associated with the disease stage, but that a raised CRP concentration occurs independently of circulating IL-6 concentrations in patients with lung cancer.