Noncovalent peptide-peptide and peptide-water interactions in small model systems were examined using an electrospray mass spectrometer equipped with a high-pressure drift cell. The results of these aggregation and hydration experiments were interpreted with the aid of molecular mechanics (MM) and density functional theory (DFT) calculations. The systems investigated include bare deprotonated monomers and dimers [P-1,P-2-H](-) and hydrated deprotonated monomers and dimers [P-1,P-2-H](-.)(H2O)(n) for the peptides dialanine (P = AA) and diglycine (P = GG). Mass spectra indicated that both peptides AA and GG form exclusively dimer ions in the electrospray process. Monomeric ions were generated by high-energy injection of the dimers into the drift cell. Temperature-dependent hydration equilibrium experiments carried out in the drift cell yielded water binding energies ranging from 11.7 (first water molecule) to 7.1 kcal/mol (fourth water) for [AA-H](-) and 11.0 to 7.4 kcal/mol for [GG-H](-). The first water molecule adding to the dimer ions [AA-H](-.)(AA) and [GG-H](-.)(GG) is bound by 8.4 and 7.5 kcal/mol, respectively. The hydration mass spectra for the monomers and dimers provide a means to compare the ability of water and a neutral peptide to solvate a deprotonated peptide [P-H]-. The data indicate that a similar degree of solvation is achieved by four water molecules, [P-H](-.)(H2O)(4), or one neutral peptide, [P-H](-.)(P). Temperature-dependent kinetics experiments yielded activation energies for dissociation of the dimers [AA-H](-.)(AA) and [GG-H](-.)(GG) of 34.9 and 32.2 kcal/mol, respectively. MM and DFT calculations carried out for the dialanine system indicated that the dimer binding energy is 24.3 kcal/mol, when the [AA-H] and AA products are relaxed to their global minimum structures. However, a value of 38.9 kcal/mol is obtained if [AA-H]- and AA dissociate but retain the structures of the moieties in the dimer, suggesting the transition state occurs early in the dissociation process. Similar results were found for the diglycine dimer.