The ability to radiolabel and follow the red cell in vivo has been of great value to the clinician and the investigator. An understanding of the advantages and disadvantages of the three nuclides used in transfusion medicine--51Cr, 99mTc, and 111In--allows the selection of the appropriate nuclide for the task at hand. For red cell life-span studies and for red cell survivals extending over one hour, 51Cr is the label of choice. The most accurate method for determining the zero-time (100% survival) point for a life span or survival study is to ascertain the RCM of the subject using autologous red cells labeled with another nuclide, preferably 99mTc. RCM studies done independently from a 51Cr survival should be performed using 111In labeled red cells. Red cell survivals are most often used to determine transfusion compatibility or to evaluate blood storage systems. There are important differences in the conduct and interpretation of red cell survivals for these two purposes. Although other promising methods for evaluating the in vivo survival of red cells are under investigation, it is likely that the radiotracers now available will continue to play a primary role in performing these studies in the future.