A method of calibrating multi-crystal, single block radiation detectors for use in positron emission tomography and other devices with multi-crystal, single block radiation detectors that are used to determine gamma ray distribution. The detector units are individually subjected to a gamma ray flood source wherein the gamma ray has an energy in excess of about 0.7 MeV, and preferably above about 1.0 MeV. Energies of up to about 10 MeV are usable with the calibration method, with higher energies giving rise to containment and handling problems because of the energy. The light produced within each of the crystals is converted to electrical signals through, for example, photomultiplier tubes. These signals are used to generate a lookup map, this map providing information as to the correct positioning and response of each crystal in the array of crystals of the block detector. The method is useful for detector blocks of of many sizes that are divided into arrays of a large number of crystals.