Direct numerical simulation (DNS) data are presented to study differentially diffusing conserved scalars in isotropic turbulence. The two scalars are initially identical but subsequently decorrelate because one is diffusing faster than the other. The main focus of the paper is the study of the time evolution and possible modeling of quantities that characterize differential diffusion. The Reynolds number dependence of the mean square of the difference of the conserved scalars (α=Z−Zf, 〈α2〉) is investigated and compared to the theoretical scaling predicted by Kerstein et al. [Phys. Fluids A 7, 1999 (1995)]. The behavior and possible modeling of the conditional average of α is studied. The recent closure method of Kronenburg and Bilger [Phys. Fluids A 5, 1435 (1977)] is further corroborated and a novel approach to the prediction of the conditional average of α is discussed.