A mathematical model has been proposed for a heterogeneous isotopic exchange reaction which involves film diffusion, surface chemical reaction and intraparticle diffusion. The exchange equation to predict the exchange fraction as a function of time for the spherical particles immersed in a solution of finite volume has been derived. The relations between the exchange fraction and dimensionless time are plotted with ε(=ak_f/KD_e, ε₁(=K₁a²/D_e) and final fractional uptake as parameters. From the values of the kinetic parameters ε and ε₁, the relative importance of each limiting step is discussed. Experimental results of the isotopic exchange reaction of calcium ion in both system CaCO₃(s)/Ca²⁺(aq) and system calcium type resin Dowex 50W-X8/Ca²⁺(aq) are coincident with the theoretical equation proposed in this study.