Pyridine and piperidine inhibited the hydrodesulfurization (HDS) of 4,6-dimethyldibenzothiophene (4,6-DM-DBT) over Pt, Pd, and Pt-Pd catalysts supported on amorphous silica-alumina. Pyridine was a stronger inhibitor at low pressure, and piperidine was a stronger inhibitor at high pressure of the nitrogen-containing compound, because pyridine adsorbs relatively more strongly on the metal and piperidine adsorbs relatively more strongly on the acidic support. Hydrogenation of partly hydrogenated sulfur-containing intermediates, as well as the removal of sulfur from the intermediates, was slowed down by piperidine and pyridine. The hydrogenation pathway in the HDS of 4,6-DM-DBT was inhibited much more than the direct desulfurization pathway. The hydrogenation of the desulfurized products 3,3'-dimethylcyclohexylbenzene and 3,3'-dimethylbiphenyl over the Pt-Pd catalyst was suppressed by piperidine and pyridine. Piperidine and pyridine strongly decreased the ability of noble metal particles to convert refractory molecules like 4,6-DM-DBT. Because the bimetallic Pt-Pd catalyst was less sensitive to pyridine and piperidine, it still had an advantage over the monometallic Pt and Pd catalysts.