We present mass spectrometric results for van der Waals clusters composed of dimethoxyethane molecules (CH3OCH2CH2OCH3 = DMEt). The protonated dimethoxyethane cluster ions (DMEtH+ were observed to form the most intense cluster ion series. A number of other cluster ion sequences including (DMEt)(n)(CH3-OHH+ and (DMEt)(n)(H2OH+ were also observed. In a separate tandem mass spectrometric study, we observe that the collision-induced dissociation spectra of (DMEtH+ (n = 1, 2) yield CH3OH2+ and H3O+ cations. This leads us to suggest that the cluster ion series (DMEt)(n)(CH3OHH+ and (DMEt)(n)(H2OH+ observed in neat expansions of dimethoxyethane arise as a result of intracluster ion-molecule reactions. The magic numbers exhibited by the intensity distributions of (DMEt)(n)(CH3OHH+ and (DMEt)(n)(H2OH+ are consistent with CH3OH2+ and (H2OH+ forming the central ion core within the cluster. This clearly indicates that the protonation site within a cluster is determined by the maximization of the number of hydrogen-bonding sites rather than proton affinity considerations alone. This also suggests that solvation of a protonated DMEt, by even a small number of solvent molecules, leads to the displacement of the internal hydrogen bond, such that the proton will reside on the molecule which would lead to the creation of the largest number of hydrogen bonding sites.