The aim of the study was to examine the main intrahepatic lymphocyte subpopulations, namely CD3(+) lymphocytes, natural killer (NK)-like T lymphocytes (NKT) expressing the CD3(+) CD56(+) phenotype, CD56(+) NK cells, CD4(+), and CD8(+) T cells in livers of patients with gastric and colorectal cancer with and without hepatic metastases. The proportion of each lymphocyte subset was determined in 34 patients with gastric or colorectal cancer (18 with and 16 without liver metastasis) by two-color flow cytometry after extraction of hepatic mononuclear cell fraction. The distribution of lymphocyte subpopulations in selected areas of liver metastases and adjacent liver tissue was evaluated using immunohistochemistry for CD4, CD8, and CD56. Flow cytometry analysis revealed a significant decrease in the proportion of CD3(+) CD56(+) cells in metastatic livers, but not in nonmetastatic livers (11.9 +/- 10.3 vs 24.2 +/- 13.6%, p = 0.02). The percentage of intrahepatic CD3(-)CD56(+) cells was also decreased in patients with metastases compared to those without (10.1 +/- 11.6 vs 16.6 +/- 8.9%, p = 0.039). Immunohistochemically, three types of lymphocytes (CD4(+), CD8(+), and CD56(+)) were present in the metastatic tissue, although the number of CD56(+) cells was almost twice lower. We found a low prevalence of tumor-infiltrating CD4(+), CD8(+), and CD56(+) cells in livers with multiple metastases, whereas in cases with solitary metastasis a higher degree of lymphocyte infiltration was observed. The number of CD3(-)CD56(+) and CD3(+) CD56(+) cells was decreased in metastatic livers compared to those unaffected by metastases. Therefore the prevalence of tumor-infiltrating lymphocytes seems to be related to the progression of metastatic liver disease. Depletion of hepatic innate lymphocytes may reveal susceptibility to metastatic liver disease and could be a reason for the escape of metastatic cells from the mechanisms of liver immune control.