A single pellet diffusion reactor (SPDR) of new design has been used to investigate the influence of nonuniform distributions of active ingredient on the Ni-catalyzed hydrogenation of benzene. Five different distributions, ranging from preferential shell-loading to uniform to preferential core loading have been studied under isothermal conditions. Analysis of results has been carried out using a simple one-dimensional diffusion/reaction analysis, which the configuration of the SPDR is set to mimic. The rate of the reaction follows an Eley-Rideal model, effectively positive fractional-order under the experimental conditions, for which kinetics the nonuniform distribution problem has not been studied experimentally before. Preferential shell-loading yields the highest catalytic effectiveness but because of the complex interactions between the reaction kinetics and the activity profiles within the pellets, there is no simple relationship between diffusion lengths and effectiveness even for large values of the Thiele modulus.