The distribution and number of seamless endothelial cells (SE) were studied in various organs and tissues of rats, rabbits and humans (1) by light microscopy after silver impregnation of the endothelial cell boundaries, (2) by electron microscopy, and (3) in three-dimensional reconstructions of duodenal villi and renal glomeruli. Since SE are situated mostly at branching points, the number of SE is roughly correlated to the number of branchings in the capillary system concerned. SE make up about 50% of all endothelial cells in the renal glomerulum and duodenal villi, and about 30% in the cerebral cortex. However, they rarely occur in bradytrophic tissues. SE have been found exclusively in net capillaries (true capillaries). They seem to be absent in most arterio-venous capillaries (capillary parts of thoroughfare channels), in the capillaries of endocrine glands, as well as in the sinusoidal systems of heart muscle, liver, spleen and bone marrow. It is concluded that SE are developed when tube formation is confined to a single endothelial cell. SE are intercalated most frequently in those capillaries that develop lastly in the terminal vascular bed. The seamless segments are canalized by fusion of intraendothelial vacuoles with pre-existing vascular walls. The existence of SE, confirming the dual structural design of capillary systems, may be used as a detector for net capillaries.