Interleukin-1 receptor antagonist (IL-1ra), an endogeneous inhibitor of IL-1, plays an immunosuppressive role in vivo by blocking the proinflammatory effects of IL-1. In the present study, we examined whether IL-1ra expression in human gastric carcinoma correlates with tumor progression and/or metastatic potential. The reverse transcription-polymerase chain reaction was used to compare the expression of the secreted form of IL-1ra (sIL-1ra) and the intracellular form of IL-1ra (icIL-1ra) mRNA in tumor and corresponding benign tissue obtained from 38 patients with gastric carcinoma. The incidence of sIL-1ra mRNA expression was significantly higher in tumor (52%) than in corresponding benign tissue (18%) (P = 0.002). On the contrary, icIL-1ra mRNA was detected in all tumors and benign tissues. The expression of sIL-1ra mRNA by malignant tissue correlated positively with both lymph node metastasis (P = 0.008) and liver metastasis (P = 0.015). There was no association between tumor sIL-lra mRNA expression and other clinicopathologic factors. The degree of regional lymph node reaction, such as sinus histiocytosis, in tumors expressing sI-1ra mRNA was significantly weaker than that in tumors without sIL-1ra mRNA expression (5/20 vs. 12/18, P = 0.010). These results demonstrate that the altered expression of sIL-1ra by malignant tissue may be related to the progression of gastric carcinoma via modulating host immune response.