Mass spectrometers designed for isotopic analyses on small samples of fuels for neutronic reactors have been used for fuel depletion studies. The design details of these instruments and the mathematical basis for data treatment are described. Studies have been performed utilizing radiochemical methods for fuel depletion determinations. Gamma ray spectrometry and radiochemical separations have been used to determine the total number of fissions induced in irradiated specimens. By combining radiochemical and mass spectrometric techniques a description of the isotopic changes in fuel specimens was obtained.