PURPOSE: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogeneous factors of human tumor progression. The aims of this study is to investigate the correlation between the expression of COX-2 and iNOS and to assess the clinicopathological significance of COX-2 and iNOS expression in patients with colorectal cancer. METHODS: One hundred and five patients, who underwent curative resection of colorectal cancer from 1994 to 1997 were analyzed retrospectively. The monoclonal antibody to the COX-2 and iNOS were used for the immunohistochemical analysis. RESULTS: In 105 patients the COX-2 and iNOS positive rate were 86.7% and 69.5% respectively. There was significant correlation between COX-2 and iNOS expression (r= 0.378, P<0.01), that is, the lesions which expressed high level of COX-2 also expressed iNOS highly. The proliferation index (Ki-67 labeling index) was correlated with iNOS (P=0.013), and the microscopic differentiation with COX-2 (P=0.004). However, the expression of COX-2 and iNOS proteins did not correlate with any other clinicopathological parameters including patient survival. CONCLUSIONS: Although the pattern of positive expression was similar in both enzymes, the expression of both enzymes was not related to prognosis in patients with colorectal cancer. But COX-2 and iNOS seems to have a role not only in carcinogenesis but also tumor cells proliferation. To evaluate the exact role of these enzymes, further studies of the apoptosis and cancer metastasis and of links between the cancer related factors of COX-2 and iNOS are warranted.