The syndrome of cachexia associated with malignant diseases can be in part attributed to the effects of tumour necrosis factor alpha (TNFalpha) which itself is produced by a variety of tumour cells. We have recently reported that the human hepatoma cell line HepG2 expresses the TNFalpha gene and releases biologically active TNFalpha protein after stimulation with interleukin-1beta (IL-1beta). Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein necessary for the proliferation and differentiation of neutrophil progenitor cells in the bone marrow. In addition G-CSF has been reported to exert anti-inflammatory effects. In our study we tested the effect of recombinant human G-CSF (rhG-CSF) on TNFalpha production in HepG2 cells. It could be shown that rhG-CSF (250 U/ml) significantly reduced IL-1beta-induced (300 pg/ml) TNFalpha gene expression after 1-h and 3-h incubation periods (TNFalpha mRNA concentrations were: 8.8+/-2.1 amol/ microg total RNA after a 1-h incubation with IL-1beta versus 3.8+/-1.3 amol/ microg total RNA after a 1-h incubation with IL-1beta + rhG-CSF and 13.8+/-2.2 amol/ microg total RNA after a 3-h incubation with IL-1beta versus 8.8+/-2. 1 amol/ microg total RNA after a 3-h incubation with IL-1beta + rhG-CSF). From these data we conclude that rhG-CSF is a potent inhibitor of cytokine-induced TNFalpha production by tumour cells. Therefore, treatment of patients with malignant diseases with rhG-CSF might represent a useful tool to improve the tumour-associated cachexia.