A new practical method has been developed for calculating neutron-activation inventories of target material in inertial fusion energy (IFE) reactors such as HYLIFE-II. It accounts for irradiation both in the target and in the internal blanket and for material circulation in and out of the primary loop. The continuous removal of target material in the real system is approximated by a batch extraction (BE). A single target is followed through its lifetime in the reactor using “transition matrices” for activation and decay which are generated by the ACAB code package. The inventory of all the isotopes of interest accumulating in the reactor is obtained by superimposing the contribution of single targets. The new BE model simulates, within minutes, the evolution of more than 150 isotopes over the 30-year reactor lifetime, explicitly accounting for the millions of neutron pulses experienced by a single target and summing the inventories of all the targets.