Conventional nuclear imaging techniques utilizing lead collimation rely on radioactive tracers with little role in human physiology. The principles of imaging based on coincidence detection of the annihilation radiation produced in positron decay indicate that this mode of detection is uniquely suited for use in emission computed tomography. The only gamma-ray-emitting isotopes of carbon, nitrogen, and oxygen are positron emitters, which yield energies too high for conventional imaging techniques. Thus development of positron emitters in nuclear medicine imaging would make possible the use of a new class of physiologically active, positron-emitting radiopharmaceuticals. The application of these principles is described in the use of a physiologically active compound labeled with a positron emitter and positron-emission computed tomography to measure the local cerebral metabolic rate in humans.