The dissociative chemisorption of CH4 on Ni overlayers on Ru(0001) has been investigated. It is found that the initial sticking probability at T = 530 K is approximately a factor of 20-30 higher on a pseudomorphic overlayer of Ni than on Ni(111) and a factor of two higher than on Ru(0001) illustrating the unique properties of metal-on-metal systems. The effect of enhanced reactivity is primarily ascribed to electronic effects induced by a straining of the Ni overlayer. The enhanced reactivity towards CH4 is accompanied by new features in the thermal desorption spectra of CO. The reactivity of the, system depends strongly on the annealing temperature. Molecular beam experiments at high translational energy are qualitatively different from thermal data showing a monotonic decrease of the CH4 sticking probability as Ni is added.