Most solid malignancies show some degree of lymphoid infiltration suggesting a specific immunologic host vs. tumor reaction. Tumor-infiltrating lymphocytes (i.e., CD3 + T-lymphocyte subsets), the human leukocyte antigen (HLA) class I molecules, and the intercellular adhesion molecule-1 (ICAM-1) are key factors involved in T-cell-mediated immune surveillance. The present study was designed to assess the expression pattern of intratumoral lymphocyte infiltrates and their relationship to HLA class I and ICAM-1 expression with regard to primary esophageal carcinoma and to evaluate their prognostic influence. Representative samples of primary tumors were obtained from 55 patients who had undergone radical en bloc esophagectomy. Frozen sections of these tumors were stained with monoclonal antibodies directed against CD3 for the assessment of tumor-infiltrating lymphocytes, HLA class I, and ICAM-1. The mean postoperative observation period was 19.5 months (range 5 to 45 months). Lymphocyte infiltration was absent in four tumors (8%), whereas 31 tumors (64%) showed moderate and 13 (27%) showed strong infiltration. HLA class I expression was deficient in 24 tumors (45%). Coexpression of HLA class I and ICAM-1 was significantly associated with lymphocyte infiltration of the tumor. Kaplan-Meier analyses revealed a significant beneficial influence on relapse-free survival for patients with lymphocyte infiltration of primary tumors compared to those with no lymphocyte infiltration of tumors (median 4 months vs. 18 months; P <0.002) and for HLA class I+ tumors compared to HLA class I- tumors (median survival >18 months vs. 7 months; P = 0.0081). The present data support the hypothesis that T-cell-mediated immunity may influence the fate of patients with esophageal cancer.