Perisinusoidal (P.S.) cells occurring in the spaces of Disse in the livers of normal cats, dogs, miniature pigs, albino rats, human adults and children were examined by electron microscopy. The ultrastructural details of the P.S. cells and their topographic relationships with hepatocytes, sinusoidal lining cells and reticulum fibers are described. Species differences between P.S. cells were primarily a dissimilarity in lipid content: the main ultrastructural features were the same in all species studied. The P.S. cells of the rat liver displayed only low endocytotic activity, and no phagosome formation following intravenous administration of horseradish peroxidase. The close topographic relationship of the P.S. cells with the intralobular reticulum fibers was reminiscent of the intimate connection between fibroblasts and collagen fibers, or, in cat liver, of the reticulum cell--reticulum fiber association seen in lymphoid organs. Fibroblasts were not found inside the hepatic lobules. These findings support the conclusion that the reticulum fibers of hepatic lobules are produced by perisinusoidal cells which, however, display also other functions.