The tumor markers Cyfra 21-1, TPA and SCC were assayed in a series of 96 patients with squamous cell carcinoma of the esophagus. Sensitivity was 42% for Cyfra 21-1, 40% for TPA and 37% for SCC. Combining Cyfra 21-1 and SCC gave a 56% sensitivity and combining TPA and SCC a 58% sensitivity. Sensitivity varied with disease stage and was particularly good in stage IV disease. Tumor markers did not vary with tumor differentiation. SCC levels were higher in tumors in the upper third of the esophagus. Pre-treatment levels of Cyfra 21-1 correlated with histological response. Cyfra 21-1 was also the only marker which distinguished significantly different survival curves. In multivariate analysis, however, treatment was the only independent factor predictive of survival.