A technique was developed that allowed the in vivo observation of Peyer's patches in the mouse for several hours. Untreated animals and animals depleted of lymphocytes were used. In this species, blood vessels associated with the lymphoid nodules are readily visible through the thin serosal muscle coat. High-endothelium venules are recognized by the large number of refractile cells that adhere to the luminal surface. A colloidal carbon suspension injected intravenously labeled high-endothelium venules and was only rarely seen in arterial and capillary segments or in venules of the gut parenchyma. When fluorescein isothiocyanate-labeled (FITC-labeled) syngeneic spleen cells were injected, they appeared in vessels of the Peyer's patch within a few seconds and began to adhere to the luminal surface of high-endothelium venules. In untreated animals, peak numbers of fluorescent cells were reached after about 20 min. Many adhered but some were swept away. In lymphocyte-depleted animals, however, peak numbers were reached after only a few minutes and most cells remained attached.