The interaction of the components of topical formulations with the skin is an important consideration for effective drug delivery and efficacy. The relative importance of solubility parameters and other solvent properties on membrane diffusion processes has not been fully elucidated in the literature. In this paper, the effect of different vehicles on the permeation of caffeine, salicylic acid and benzoic acid through silicone membranes was evaluated. Polydimethylsiloxane membranes were used as model membranes for comparing the release characteristics of saturated solutions of model permeants because of their homogeneity and uniformity. Log P (octanol-water partition coefficient) and solubility parameter values were calculated for the compounds under study. In vitro diffusion studies indicated that the permeation profiles of all solutes showed a similar pattern. The permeation rates of benzoic acid and salicylic acid through silicone membrane from saturated solutions were higher than those for caffeine reflecting the more lipophilic nature of these compounds in comparison with caffeine. Solvent uptake studies confirmed that the vehicles that were highly sorbed by the membrane altered its properties and hence the flux. Vehicles that were not sorbed by the membrane showed similar steady-state fluxes for the model drugs. This suggests that the diffusion process is mainly influenced by the interactions between the vehicles and the membrane. Solubility parameter alone cannot explain the interactions between the membrane and the vehicles in all cases. Rather, it is likely that membrane flux reflects a combination of different solvent and solute characteristics, such as size, shape and charge distribution.