The reliability of radiation dose estimates in internal radionuclide therapy is directly related to the accuracy of activity estimates obtained at each imaging time point. The recently published MIRD pamphlet no. 23 provided a general overview of quantitative SPECT imaging for dosimetry. The present document is the first in a series of isotopespecific guidelines that will follow MIRD 23 and focuses on one of the most commonly used therapeutic radionuclides, 131I. The purpose of this document is to provide guidance on the development of protocols for quantitative 131I SPECT in radionuclide therapy applications that require regional (normal organs, lesions) and 3-dimensional dosimetry. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.