The dissociation of CO serves both as a model test reaction on single crystals and as a relevant reaction step for industrial methanation. We combined extensive density functional theory calculations, ultra-high vacuum experiments on well-defined single crystals, and catalytic activity measurements on supported catalysts in a study of the dissociation mechanism of CO on Ni surfaces. We found that this process is highly structure-sensitive and also is sensitive to the presence of hydrogen: Under ultra-high vacuum, with no hydrogen present, the dissociation proceeds through a direct route in which only undercoordinated sites (e.g., steps) are active. Under methanation conditions, the dissociation also proceeds most favorably over undercoordinated sites, but through a COH species. (c) 2008 Elsevier Inc. All fights reserved.