A method for analyzing the changes in the neutronic characteristics of large fast reactors during long-term operation is developed. The nonuniform buildup and depletion of the fuel nuclides is taken into account by using eigenfunction expansions in the solution of the one-dimensional, multigroup diffusion equations. A refueling scheme is introduced to study the behavior over many reloading cycles as well as between two loading events. The depletion of fissile nuclides in the core and the buildup of fissile nuclides in the blanket cause a power shift into the blanket. The effect of this power shift on the breeding ratio, the power density, and the reactivity coefficients of a large mixed-oxide fast reactor is explored in detail. The power shift into the blanket during the approach to equilibrium is 1.55% of the total reactor power. The breeding ratio increases by only 0.56% during reactor operation. The sodium void coefficient increases by 11.2% from startup to the end of an equilibrium period. The Doppler coefficient, which changes only slightly during the approach to equilibrium, becomes more negative. The total change in the Doppler coefficient is <2%.