Recent predictive equations for evaluating the value of diffusion coefficients, developed for two hard sphere-solvent systems, have been extended to n-hard-sphere-solvent systems. This model has been used to predict the diffusion behavior of nonionic polymer-solvent mixtures as a first-order function of volume fraction from the knowledge of the distribution function. Hence, the entire diffusion matrix for polydisperse systems, which include both main- and cross-term diffusion coefficients, has been built up for the first time. The main-terms diffusion coefficients D-ii are mostly affected by the variation in viscosity. The magnitude of the cross-term diffusion coefficients D-ij is strictly related to the abundance and diffusivity of solute i and to the molecular volume corresponding to solute j. The predicted diffusion coefficients have been used to calculate the apparent, average diffusion coefficients, which are compared with the experimental values measured by the Gouy interferometry method in the case of the poly(ethylene glycol) homologous series. The agreement between the calculated and experimental Gouy parameters is good. The cross-term diffusion coefficients are found to be significant in the calculation of the apparent diffusion coefficient for a polydisperse solute. Some comments on the study of ternary systems containing a polydisperse solute are done.