X-ray photoelectron spectroscopy and first-principles density-functional calculations were used to study the interaction of thiophene, H2S, and S-2 with Ni2P(001), alpha-Mo2C(001), and polycrystalline MoC. In general, the reactivity of the surfaces increases following the sequence MoC < Ni2P(001) < alpha-Mo2C(001). At 300 K, thiophene does not adsorb on MoC. In contrast, Ni2P(001) and alpha-Mo2C(001) can dissociate the molecule easily. The key to establish a catalytic cycle for desulfurization is in the removal of the decomposition products of thiophene (C.,H,, fragments and S) from these surfaces. Our experimental and theoretical studies indicate that the rate-determining step in a hydrodesulfurization (HDS) process is the transformation of adsorbed sulfur into gaseous H2S. Ni2P is a better catalyst for HDS than Mo2C or MoC. The P sites in the phosphide play a complex and important role. First, the formation of Ni-P bonds produces a weak "ligand effect" (minor stabilization of the Ni 3d levels and a small Ni -> P charge transfer) that allows a high activity for the dissociation of thiophene and molecular hydrogen. Second, the number of active Ni sites present in the surface decreases due to an "ensemble effect" of P, which prevents the system from deactivation induced by high coverages of strongly bound S. Third, the P sites are not simple spectators and provide moderate bonding to the products of the decomposition of thiophene and the H adatoms necessary for hydrogenation.