To understand the interaction between toluene and methanol, the chemical reactivity of {(C6H5CH3)-(CH3OH)(n=1-7)}(+) cluster ions has been investigated via tandem quadrupole mass spectrometry and through calculations. Collision Induced Dissociation (CID) experiments show that the dissociated intracluster proton transfer reaction from the toluene cation to methanol clusters, forming protonated methanol clusters. only occurs for n = 2-4. For n = 5-7. CID spectra reveal that these larger clusters have to sequentially lose methanol monomers until they reach it 4 to initiate the deprotonation of the toluene cation. Metastable decay data indicate that for n = 3 and n = 4 (CH3OH)(3)H+ is the preferred fragment ion. The calculational results reveal that both the gross proton affinity of the methanol subcluster and the structure of the cluster itself play an important role in driving this proton transfer reaction. When n = 3, the cooperative effect of the methanols in the subcluster provides the most important contribution to allow the intracluster proton transfer reaction to occur with little or no energy barrier. As n >= 4, the methanol subcluster is able to form ring structures to stabilize the cluster structures so that direct proton transfer is not a favored process. The preferred reaction product, the (CH3OH)(3)H+ cluster ion, indicates that this size-restricted reaction is driven by both the proton affinity and the enhanced stability of the resulting product.