Rare cases of graft-versus-host disease after liver transplantation indicate that donor lymphocytes may be transferred to the recipient by human liver grafts. In this study, we have analyzed the number and subpopulations of donor lymphocytes transferred by liver grafts in order to evaluate the potential relevance of these cells after transplantation. Therefore, mononuclear cells were isolated from the tissue of perfused human donor livers and from the associated lymph nodes. The number of lymphocytes, their location, and surface marker expression were determined by immunostaining. The majority of lymphocytes transferred by the grafts were found within the liver tissue (5.3 +/- 2.9 x 10(9) cells). These lymphocytes are mainly T and NK cells, predominantly CD8+, are partially activated (28% HLA-DR+), and show strong adhesion molecule expression (88% LFA-1(3+)). In addition, 20-500 x 10(6) of resting lymphocytes, predominantly T and B cells, are transmitted by lymph nodes. These findings demonstrate that considerable numbers of donor lymphocytes of distinct phenotype are regularly transmitted to the recipient by human liver grafts and may be of functional relevance after transplantation.