Highly lipophilic basic drugs, the antiestrogens AE1 and AE2 shall be delivered transdermally. DSC as an additional tool in combination with classic investigation techniques should be used to clarify permeation enhancement. Skin treatment with pure solvents, polyethyleneglycol (PG) and dimethylisosorbide (DMI), slightly changed the phase transition temperatures. Formulations containing lauric acid markedly shifted these transitions to lower temperatures, indicating a lipid-fluidising action of lauric acid. In those cases an additional endothermic peak was observed around 40°C, which is attributed to the melting of crystalline lauric acid. Since the DSC program started at -20°C, it is very likely that lauric acid in the skin samples crystallized. A formulation of polyethyleneglycol and lauric acid leads to significantly higher deposition of lauric acid into the skin, in opposition to dimethylisosorbide/lauric acid formulation. These findings correspond to the results from our in-vitro permeation studies, where a significantly higher transdermal steady-state flux of lauric acid from polyethyleneglycol-formulation in comparison to dimethylisosorbide-formulation was observed. By this unique combination of polyethyleneglycol and lauric acid, the barrier is obviously modified in a way, which allows the highly lipophilic antiestrogens to permeate easily through the skin. So, from this formulation steady-state fluxes of AE-1 were observed, representing approximately the same value compared to the unhindered permeation through skin without stratum corneum. The grade of temperature shift on the skin lipids to lower temperatures can be correlated with softening effects and the enhancement potential of the formulation.