The applicability of NiW- and Pt-based catalysts for the deep hydrodesulfurization (HDS) of diesel fuel was evaluated from gas phase experiments with the model reactants DBT (dibenzothiophene), 4MDBT (4-methyl dibenzothiophene), and 4E6MDBT (4-ethyl, 6-methyl dibenzothiophene). NiW/Al2O3 is less active than NiMo/Al2O3 in DBT HDS, but more active in 4E6MDBT HDS because of its greater hydrogenation activity. Replacing Al2O3 by ASA (amorphous silica-alumina) causes a general lowering of the activity under H2S-free conditions, but induces a dramatic increase in the H2S tolerance of NiW. Thus, the activity of NiW/ASA was much higher than that of NiMo/ASA or NiMo/Al2O3 during 4E6MDBT HDS in the presence of 0.2% H2S. The higher activity over the acidic supports could not be attributed to dealkylation or isomerization; however, it was associated with C-C bond scission in the thiophenic ring, either before or after the desulfurization step. Pt/ASA has DBT and 4MDBT HDS activities which are comparable with those of the NiW catalysts; in 4E6MDBT HDS Pt/ASA is much more active because of its superior hydrogenation activity. Its sulfur tolerance, on the other hand, is much lower than that of NiW catalysts, rendering Pt/ASA less active than NiW/ASA during 4E6MDBT HDS in the presence of 0.2% H2S.