Synergetic effects in hydrodesulfurization (HDS) have been investigated in operating conditions different from all those mentioned in literature yet. A synergism is observed between Co(x)/γ-Al2 O3 or Ni(x)/γ-Al2O3, and Mo(y)/γ-Al2O3 beds separated by a 5 mm of γ-Al2O3 or SiO2 bed. The results were obtained in conditions very close to those of industrial processes, namely using a high-pressure continuous-flow-reactor and gas-oil as feed, in contrast to model feeds used in most similar experiments. Compared to the activity of the individual beds, a significant increase of HDS activity is observed at 325, 350 and 375 °C, in the case of Co and Ni. As the Co (Ni) containing beds are physically separated from each other, no mutual contamination susceptible to lead to the formation of Co-Mo-S or Ni-Mo-S is possible. Several other alternative explanations have been examined, but it seems that the logical conclusion is that spillover of hydrogen could explain the phenomenon. No synergetic effect was detected using SiC as separator. The effects of changes in the cobalt or nickel (x), and molybdenum (y) contents and of the reaction temperature over the synergetic effect are also described and discussed. The effect of a diffusion of spillover species (probably hydrogen Hso) over a 5 mm distance is so conspicuous that it seems difficult to rule out an important flow of Hso and thus a much stronger effect in real CoMo and NiMo catalysts where the sulfided elements are at nanometer distances from each other. This makes even reasonable the hypothesis that hydrogen spillover could actually play an essential role in the HDS reaction over molybdenum-containing catalysts.