Interleukin (IL-18) and nitric oxide (NO) are immunoregulatory cytokines that have been suggested to participitate in the multistep process of carcinogenesis. In this study, serum IL-18 and nitrite+nitrate levels (as an index of NO generation) were measured in 26 patients with histologically confirmed renal cell carcinoma (RCC) before surgical procedure and in 8 healthy controls. RCC patients showed significantly higher serum IL-18 levels when compared to the control subjects (P<0.001). Serum IL-18 levels were found to be similar in patients with T1 and T2, T3, T4 tumors (p>0.05). Patients with grade 3 and 4 tumors showed significantly higher serum IL-18 levels when compared to the patients with grade 1 and 2 tumors (p<0.05). No significant difference was found in serum nitrite+nitrate levels between RCC patients and control subjects (p>0.05). Serum nitrite+nitrate levels were lower in patients with grade 3 and 4 tumors than those with grade 1 and 2 tumors, but this was not statistically significant (p=0.063). In conclusion, elevated serum level of IL-18 in RCC patients than in controls and extra-increase of this level in those with high grade tumors may reflect the degree of human defence mechanisms against tumor cells in RCC.