We have studied the structure and reactivity of the acetone-methanol cluster series {(C3H6O)m(-CH3OH)(n)}H+ as a function of cluster size. Conventional mass spectra are mainly dominated by the three series of protonated acetone-methanol cluster ions, (C3H6O)(m) = (1-3)(CH3OH)(n)H+. In the CID spectra of the (C3H6O)(1)(CH3OH)(n)H+ series, we observed two different reaction channels: the loss of CH3OH and the loss of C3H6O. The former dominates regardless of the cluster size. For the (C3H6O)(2)(CH3OH)(n)H+ series, the CID result reveals a change in the preferred reaction pathway as a function of cluster size. For the (C3H6O)(3)(CH3OH)(n)H+ series, the loss of C3H6O dominates. (C) 2011 Elsevier B.V. All rights reserved.