We report a joint experimental and theoretical study of the gas-phase reactivity of Al cluster anions with ethanethiol (EtSH) in a fast-flow tube reactor. Nearly all Al-n(-) clusters observed are reactive at the presence of sufficient EtSH molecules with minor exceptions. Sulfide species AlnSm- dominate the observed reaction products, indicating C-S bond activation of EtSH. By using DFT calculations we provide an in-depth analysis on the interesting cluster reactivity of Al-n(-) with EtSH. It is demonstrated that the desulfurization leading to AlnSm- products is associated with the dehydrogen processes successively initiated by S-H bond cleavage and C-H bond cracking. (C) 2013 Elsevier B. V. All rights reserved.