A three-dimensional PET detector of a type having a scintillation crystal and first and second photosensitive detectors arranged one at each opposite end face of the crystal for detecting scintillation interactions within the crystal is calibrated to determine a depth-of-interaction (DOI) function thereof by irradiating the crystal to cause a predetermined distribution of interactions along a depth axis of the crystal, and applying probability theory to signal data collected by the two photosensitive detectors. The method provides a DOI function that indicates DOI position as a function of a signal ratio R obtained from the signal data.