We report a 65-year-old man with malignant pleural mesothelioma that produced granulocyte colony-stimulating factor (G-CSF) and other cytokines. At the first presentation, the WBC count was 8600 cells/microl and C-reactive protein (CRP) was 0.6 mg/dl. Seventeen months later, the WBC count had increased to 53,600 cells/microl (93% neutrophils) and CRP to 27.1 mg/dl. The serum concentration of G-CSF had increased to 36.0 pg/dl (normal range, <5.0 pg/dl), interleukin 1beta (IL-1beta) to 46.0 pg/dl (normal range, <10 pg/dl), and IL-6 to 197 pg/dl (normal range, <4.0 pg/dl). The patient died 19 months after the first presentation, and 6 weeks after sudden leukocytosis. At autopsy, a diagnosis of malignant pleural mesothelioma was made. The tumor cells were positive for anti-human G-CSF, granulocyte-macrophage colony-stimulating factor, IL-1beta, and IL-6 antibodies. Malignant mesothelioma may produce G-CSF and other cytokines. Mesothelial cells may have the potential to produce G-CSF and other cytokines in the progress of malignant formation, and this may be a factor influencing the poor prognosis.