The influence of solvent on the conformational flexibility of o-phosphorylcholine, CH3PO4-CH2CH2N(CH3)(3)(+), and of o-phosphorylethanolamine, CH3PO4-CH2CH2NH3+, model compounds for the two most common phospholipid headgroups (PC and PE), was explored using molecular dynamics calculations based on a microscopic model with full atomic details. The potential of mean force about the principal dihedral angle, O-C-C-N, was calculated for the model compounds in vacuum and in bulk water using the umbrella sampling technique. Tn vacuum, the trans conformation is unstable and strongly disfavored with respect to the gauche conformation due to the loss of intramolecular electrostatic interactions. In bulk water, the influence of solvent results in a stabilization of the trans conformation yielding trans/ gauche energy differences of +1.5 and +0.02 kcal/mol for the model compounds of PC and PE, respectively. This result is in qualitative agreement with experimental NMR estimates from an analysis based on J-coupling constants due to Akutsu and Kyogoku (Chem. Phys. Lipids 1977, 18, 285-303) and Hauser (Biochemistry 1980, 19, 366-373). To further understand the nature of solvation effects, the dihedral potential of mean force is calculated for model systems in which the solvent is represented, first, by a vacuum continuum dielectric constant and, second, by a small number of explicit perimary hydration water molecules solvating the phosphate and nitrogen groups. It found empirically that a vacuum continuum dielectric constant of 80 or the presence of 20 explicit primary waters is sufficient to stabilize the trans conformation and reproduce qualitatively the influence of bulk solvation. This suggests that the solvent-induced increased intramolecular conformational flexibility may be equivalently interpreted in terms of continuum dielectric shielding or solvent structure effects by the primary hydration shell. The conformational flexibility of the molecules is further characterized by estimating the transition rate constants between the stable conformations in bulk solvent.