The level of expression and cellular localization of isoenzymes of nitric oxide synthase (NOS) was detected in human stomach tumor tissues. Tumor tissues showed 70% higher activity of NOS than that of normal tissues (P < 0.01). Poorly differentiated adenocarcinoma tend to have higher activity (P < 0.05) than well differentiated and moderately differentiated tumor tissues. Aminoguanidine (AG), 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), NG-monomethyl-L-arginine (L-NMMA), and Nomega-nitro-L-arginine (L-NNA) inhibited NOS activity in tumor tissues by 18, 14, 11 and 13%, respectively. The TNF-alpha mRNA expression was correlated with the inducible NOS (iNOS) level, which was high in adenocarcinomas and low in normal tissues. Tumor tissues showed higher expression of iNOS in gland epithelial cells but the level of eNOS was significantly decreased with an exception of concentrated localization in the proliferating capillary endothelium. These results revealed that isoforms of NOS might contribute differentially to growth and progression of human stomach tumor.