We have studied the size-selective reactivity of Al n − clusters with formaldehyde to determine if carbonyl bonds may be broken by complementary active sites. Gas phase experiments reveal that Al n − , where n = 8−12, react with formaldehyde to form Al n−2 CH 2 − , which demonstrates that the carbonyl bond is broken in the reaction with the cluster, while Al 13 − is found to be resistant to reaction. The most likely leaving group is determined to be Al 2 O. We also found n = 15−19 to be reactive with the products being a mix of Al n−2 CH 2 − and Al n (OCH 2 ) m − . Theoretical investigations find that the adjacent Lewis acid and Lewis base sites stabilize the resonance structure in which the carbonyl is reduced to a single bond which encourages carbonyl cleavage. A transition state analysis of the cleavage of the carbonyl bond confirms the size selective cleavage of the carbonyl bond and supports the importance of complementary Lewis acid−Lewis base active sites in governing the reactivity.