High-endothelium venules of mouse Peyer's patches were examined by scanning electron microscopy, and a quantitative assessment was made of the location of lymphocytes in relation to endothelial cells. Untreated mice and mice with markedly depressed levels of circulating lymphocytes were used. Lymphocytes were divided into adhering and migrating cells and as to association either with the body of the endothelial cell or with its cell border. Over 90% of all adhering cells and the great majority of migrating lymphocytes were located at the cell border. The exception was one animal in which most migrating lymphocytes appeared to penetrate the endothelial cells. Our data lend strong support to the currently held view that most migrating lymphocytes traverse the endothelium by following an intercellular path but that, under certain conditions, lymphocytes may penetrate the cytoplasm of endothelial cells.