Recent studies strongly suggest that the liver plays an important immunoregulatory role. Evidence of its role in general immune responsiveness originates from observation that, in recipients of liver grafts, the survival of other allografts is significantly prolonged. The question arises as to which blood lymphocyte subsets, most likely to be responsible for this phenomenon, marginate in liver sinusoids. To study this problem, a liver ex vivo perfusion model was designed for rats. In situ W/WAG livers were washed clear of sinusoidal marginating cells prior to and after 1 h perfusion with syngeneic blood. The number of blood cells retained in liver sinusoids, their phenotypes, the responsiveness to mitogen (PHA, 90 micrograms/ ml) and cytotoxicity against YAC-1 tumour cells were examined. Our studies showed that rat liver retains in the sinusoids a population of blood cells, enriched in NK, CD8+ and MHC class II+ cells, displaying a high cytotoxic activity and low responsiveness to mitogen stimulation, with a capacity of about 10(6) cells/g of tissue.