Studies have shown rat natural killer (NK) cells to be large granular lymphocytes (LGL). Analysis of the cell surface phenotype of these cells using monoclonal antibodies has demonstrated a sharing of antigens with both T cells and monocytes. The in vivo administration of these antibodies, X-irradiation, or diethylstilbesterol (DES) caused a marked depression in NK activity. The in vivo and in vitro reactivity of these animals, however, could be returned to near normal levels by the in vivo transfer of LGL but not with T cells or monocytes. Studies investigating the homing patterns of LGL and T cells have demonstrated a pattern of migration consistent with the organ distribution of these cells. A low percentage (1-3%) of LGL migrated to the site of a growing tumor. Another cell in the spleen which is morphologically similar to LGL is the large agranular lymphocyte (LAL). Our recent studies have shown that LAL are 1) found in the spleen and bone marrow, 2) antigenically very similar to LGL and 3) isolate with LGL but do not bind or kill tumor targets. We have also examined the appearance of spontaneous LGL leukemias in F344 rats. Analysis of these tumor lines indicate a great deal of morphological, histochemical, functional and antigenic similarity to LGL.