Vitamin D3-derivatives are known to be effective in differentiation and proliferation of epidermal cells. However, under certain circumstances, they also may show a hypercalcamic activity which can be a serious limitation in their use for dermatological application. For keeping small the negative side effects of vitamin D3-derivatives and for increasing the drug concentration in the skin we investigated their incorporation in liposomes to optimize their use for psoriasis treatment. The incorporation of vitamin D3-derivatives in liposomes of different lipid composition was studied by HPLC, DSC and freeze-fracture electron microscopy. Incorporation rates of more than 80% of the offered drug were found with significant variations related to the number of hydroxyl-groups in the A-ring, opened or closed B-ring, and some modifications in the side chain of the steroid-molecules. In general, the incorporation rates in egg-PC liposomes have been of about 3% up to 10% higher than in DMPC liposomes. Results, obtained by DSC and freeze-fracture electron microscopy, show a depression of the phase transition of DMPC bilayers by incorporation of vitamin D3 already at a concentration of 10 mol%. These results support the idea that vitamin D3 and its analoga investigated are incorporated into the lipid bilayer modifying there the lipid-lipid interactions.