Density functional theory and small-core, relativistic pseudopotentials were used to look for symmetric and asymmetric transition states of the gas-phase hydrolysis reaction of uranium hexafluoride, UF6, with water. At the B3LYP/6-31G(d,p)/SDD level, an asymmetric transition state leading to the formation of a uranium hydroxyl fluoride, U(OH)F-5, and hydrogen fluoride was found with an energy barrier of +77.3 kJ/mol and an enthalpy of reaction of +63.0 kJ/mol (both including zero-point energy corrections). Addition of diffuse functions to all atoms except uranium led to only minor changes in the structures and relative energies of the reacting complex and transition state. However, a significant change in the structure of the product complex was found, significantly reducing the enthalpy of reaction to +31.9 kJ/mol. Similar structures and values were found for PBEO and MP2 calculations with this larger basis set, supporting the B3LYP results. No symmetric transition state leading to the direct formation of uranium oxide tetrafluoride, UOF4, was found, indicating that the reaction under ambient conditions likely includes several more steps than the mechanisms commonly mentioned. The transition state presented here appears to be the first published transition state for the important gas-phase reaction of UF6 with water.