Leukocyte subsets that infiltrated into unmodified LEJ(RT1j)2 liver grafts from WKAH(RT1k) hosts were studied. This strain combination is fully allogeneic and yields acute rejections in skin and kidney transplantations. On days 3, 7, and 14, cellular infiltrates gradually increased, and many hepatocytes were degenerative and lost cellular glycogen. Blastoid lymphocytes were frequently seen, and mitotic features of hepatocytes were prominent (on day 14, 3 to 4/10 high-power fields). Later, on days 30, 50, and 300, the cellular infiltrates gradually subsided, and blastoid lymphocytes were rarely seen. Throughout the course, Ia+ cells (RT1.Dk+ and/or RT1.B+ cells) were the major cell populations infiltrating into the grafts. Most of the host RT1.D+ cells were histiocytoid in appearance on immunoelectron microscopy. Histiocytoid cells were the most numerous infiltrating cells, constituting 30-50% of the total infiltrating cells. There were different distributions of T cell subsets between the portal and sinusoidal areas, as we previously observed in acutely rejected rat renal allografts. Both RLyt-1+,2-(Th) and RLyt-1+,2+(Tc/s) cells were found almost equally in the portal area, while RLyt-1+,2+(Tc/s) cells predominated over RLyt-1+,2-(Th) cells in the sinusoidal area. However, a gradual replacement of RLyt-1+,2-(Th) cells by RLyt-1+,2+(Tc/s) cells, as seen in the perivascular area of renal grafts, was not found in the portal areas of the liver grafts. Except for the latter finding, the pattern of cellular infiltrates was similar to that of acute renal rejection, and the significance of these cellular infiltrates is discussed.