The epidermal growth factor receptor (EGFR) level in 56 esophageal cancer tissues was measured by 125I-EGF binding assay to elucidate its role in tumor progression. The survival rate of patients with high EGFR level (more than 50 fmol/mg protein) was significantly lower than that of patients with low EGFR level (less than 50 fmol/mg protein, P less than 0.01), although a correlation between EGFR level and the pathologic findings was not observed. The expression of EGF was examined immunohistochemically using anti-EGF monoclonal antibody in 100 esophageal cancer tissues; EGF-positive tumor cells were detected in 92.0%. The immunoreactivity of EGF was classified arbitrarily into four grades according to the number of stained tumor cells. The expression of EGF significantly correlated with the differentiation of esophageal squamous cell carcinoma (P less than 0.01, by chi-square test). The survival rate of patients with high EGF immunoreactivity (Grade 2 or 3) was much lower than in those with lower grade (0 or 1) tumors, (P less than 0.01). Patients with both high EGFR level and EGF immunoreactivity had a much worse prognosis than if both were low. Furthermore, the mitotic index was higher in groups with both high EGFR and EGF than if both were low (16.39 +/- 5.35 versus 6.90 +/- 3.31). These results suggest that EGF and EGFR in the autocrine system may play an important role in tumor progression in esophageal cancer and their expression could be of prognostic significance.