Cyclo-oxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostanoids. COX-2 expression has been found in many malignancies. This study analyzed the correlation between COX-2 expression and angiogenesis or apoptosis in human esophageal carcinomas. The study examined the expression of COX-2 in six esophageal carcinoma cell lines and in 100 esophageal squamous cell carcinomas, comparing intratumoral microvessel density (IMVD) and apoptotic index (AI) by immunohistochemistry and TUNEL methods. COX-2 was variably expressed in all the cell lines examined. COX-2 immunoreactivity was observed mainly in the cytoplasm of carcinoma cells. Significantly higher mean IMVD and lower AI were noted in the 51 strong COX-2 expressing cases than in the 49 weak cases. IMVD and AI were negatively correlated. COX-2 expression was higher in the tumors with lymphatic invasion than in the others. These data indicate that COX-2 expression is associated with increased intratumoral microvessels and suppression of tumor cell apoptosis. Thus COX-2 might play an important role in the angiogenesis and regulation of apoptosis in esophageal squamous cell carcinomas.