Hydrodesulfurization (HDS) of gas oil (GO), light cycle oil (LCO) and a model sulfur compound 4,6-dimethyldibenzothiophene (4,6-DMDBT) was compared over a series of six commercial and laboratory-made catalysts. The difference between the HDS activities of the catalysts for the model compound and the real feed stocks indicates their sensitivity to the intrinsic inhibitors (aromatics and H2S) present under industrial conditions. A severe inhibition of H2S on NiMo catalysts should be noted. Detailed analysis of the HDS products from the model feed provided information on the reaction pathways involved over the present catalysts and how they are modified in presence of inhibitors. Complementary standard tests with other model compounds were examined to determine the Bronsted acidity and hydrogenation activity of each catalyst. Such activities and their relationship explain the differences in performance of the catalysts and the relative importance of the respective reaction pathways in the HDS. Isomerization and dealkylation of 4,6-DMDBT took place prior to the desulfurization over the CoMo on the acidic support enhancing the desulfurization. Moreover, such a pathway was inhibited strongly by the aromatic partners and lost stationary activity by coke formation.