Large granular lymphocytes (LGLs) differ from other lymphocytes in their recirculation pattern and are distributed preferentially in nonlymphoid organs such as the liver and lung. The liver-associated LGLs adhere strongly to the sinusoidal endothelium and show a natural killer (NK) cytotoxicity against incoming metastatic tumor cells; this reaction occurs very rapidly because, in contrast to the immune response, it does not require complex processes in the lymphoid tissue. They have been extensively studied morphologically in terms of pit cells. LGLs have two characteristic cell organelles which participate in the NK cytolysis, i. e., dense granules and rod-cored vesicles. The former are lysosomes derived from multivesicular bodies and contain pore-forming proteins. The latter are the secretory vesicles exclusively seen in LGLs and are markedly increased in number when the NK function is augmented by biological response modifiers. These two structures are believed to be exocytosed in the space between LGL and the conjugated tumor cell. The microenvironment of the liver sinusoids, which includes Kupffer cells, endothelial cells and other lymphocytes, is considered to regulate the function of the liver-associated LGLs. Liver-associated LGLs, as well as Kupffer cells, are intrinsically involved in the defense system of the liver under various physiological and pathological conditions.