We have investigated the gas-phase reactivity of silver clusters with ethanethiol in a fast-flow tube reactor. The primary cluster products observed in this reaction are AgnSH- and AgnSH2-, indicating C-S bond activation, together with interesting byproducts H3S- and (H3S)(2)(-). Ag-n(-) clusters with an odd number of valence electrons (n = even) were observed to be more reactive than those with an even number of electrons-a feature previously only observed in the reactivity of Ag-n(-) with triplet oxygen, indicating that radical active sites play a role in their reactivity. Furthermore, the reactivity dramatically increases with large flow rate of ethanethiol being introduced in the flow tube. Theoretical investigations on the reactivity of Ag-13(-) and Ag-8(-) with ethanethiol indicate that both Ag-13(-) and Ag-8(-) face significant barriers to reactivity with a single ethanethiol molecule. However, Ag-8(-) reacts readily in a cooperative reaction with two ethanethiol molecules, consistent with the dramatic increase in reactivity with a large flow rate. Further hydrogen-transfer reactions may then release-an ethylene molecule or an ethyl radical resulting in the observed AgnSH- species.