The partition coefficient of a compound between water and an organic phase (often n-octanol) is the most frequently used descriptor in biological structure activity relationships. Despite many attempts to develop a reliable and generally applicable method to calculate partition coefficients, certain classes of compound, such as tautomers, zwitterions and flexible compounds, have proved difficult to treat using these techniques. We have extended existing methods based on the additivity of molecular fragments and the use of solvent exposed surface areas, to investigate the effects of molecular flexibility on partitioning. Our initial model assumed a linear relationship between the solvent exposed area of a fragment and its interaction with the environment. By parameterisation based on small, rigid molecules, area related fragmental values were derived for transfer from gas to water, and water to octanol. In order to calculate partition coefficients for flexible molecules, an ensemble of gas phase conformations was generated using molecular mechanics, and the solvation energy of each conformation in both water and octanol calculated. Summing the Boltzmann weighted energies of each conformation in a each phase, allowed the calculation of the free energy of the molecule in either phase, and thus the calculation of its partition coefficient. Calculations were compared with experimental data for a series of dipeptides. In order to improve our model of solvation for hydrophilic groups, the linear dependence on exposed surface area was replaced by a stepped dependence. The number of steps used for each particular group was based upon literature values of the number of water molecules that could specifically hydrate it. Improved results for both partitioning, and hydration energies were achieved for small molecules, while the dipeptides showed a wider scatter of results. In a further extension of our model designed to include the effects of entropy, we replaced our original description of the potential energy surface by one derived from a Metropolis Monte Carlo simulation. By incorporating the area dependent solvation terms before the acceptance step of the simulation we were able to simulate both phases independently, and thus to calculate partition coefficients. Good agreement was achieved with experimental results particularly using the step model of solvation. Although our approach should be capable of reproducing the difference in partition coefficients between pairs of diastereoisomers, attempts to confirm this have proven inconclusive.