Increased cyclooxygenase-2 expression has been reported to be a poor prognostic indicator in a number of cancers. In this study we investigated the relationship between COX-2 expression in squamous cell carcinoma of the esophagus and tumor characteristics and patient survival. The study group consisted of 90 men and 48 women who underwent esophagectomy for squamous cell carcinoma of the esophagus between October 1984 and May 1985. COX-2 expression was measured by immunohistochemistry in 138 primary cancers, 23 metastatic lymph nodes and 21 normal esophageal stumps. The relationship between the extent of staining for COX-2 and clinicopathological features and survival was determined. The extent of staining for COX-2 in both primary and metastatic cancers was higher than in normal squamous epithelia (P = 0.002 and P < 0.0001 respectively), and the grade of staining in the primary tumor correlated positively with the finding of lymph node metastases (P = 0.03). The 5-year survival rate in patients with less than 10% COX-2 positive cells was 47.5% compared to 23.2% in patients with more than 10% COX-2 positive cells (P = 0.0036). The relationship between survival and COX-2 staining was not due to COX-2 being a surrogate marker for TNM stage. Our results show that the expression of COX-2 is elevated in squamous cell carcinoma of the esophagus compared to normal epithelium and correlates with lymph node metastases. Survival was longer in those patients whose tumors expressed lower levels of COX-2.