This study looks at the application of 51Cr labeling of lymphocytes as a method of obtaining in vivo information about the lymphocyte in human beings. Lymphocytes were separated from whole blood by methods based on isopycnic and rate zonal centrifugation techniques and the conditions for 51Cr uptake by the separated lymphocytes standardized to enable a known amount of radioactivity to be injected into the subjects under study. The uptake of the label into various sites in the body was studied by the means of surface probes linked synchronously to a digital printout device and the survival in the circulation estimated by scintillation counting of blood samples taken at various times after injection of the label. The in vivo studies of survival and migration in 10 normal subjects show an initial rapid clearance of cells from the circulation associated with an uptake of cells into spleen and liver sites, and to a lesser extent, into sites over bone marrow and the abdomen. Survival of the circulating lymphocytes after this period appears to be relatively short, with a half-life of 1.7 days. As the available evidence suggests, this short life may be due to the differential trapping of short-lived lymphocytes in the circulation at the expense of the long-lived lymphocytes. Kinetic interpretations of the data indicate an inverse exponential uptake of cells into the sites studied, and the decline over the organs appears to follow the death rate of the cells in the body as a whole. Comparisons with studies in patients having chronic lymphatic leukemia show a relative inability of leukemic lymphocytes to leave the circulation and enter some sites in the body. These preliminary studies indicate the potential of 51Cr labeling as a useful clinical research tool in the study of lymphocytes in human beings.