To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polymerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-alpha, IL-6, IL-1 beta, and IFN-gamma mRNAs were found in the livers of patients with extrahepatic diseases. TNF-alpha and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-alpha in the sera and TNF-alpha mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.