Flexible lipid vesicles have shown promise as a means of transdermal drug delivery, potentially complementing or even ultimately replacing current needle injection methods. Vesicles are made flexible by incorporation of a surfactant at moderate amounts into the formulation. While surfactant addition increases the apparent flexibility of vesicles, it may also alter vesicle stability. We are studying changes in the size and apparent flexibility of lipid vesicles with varying surfactant concentration over a six-week period. The effects of these changes on vesicle permeation of a skin-like barrier are also being tested. Flexible lipid vesicles are prepared using the lipid, egg phosphatidylcholine (egg-PC) and the nonionic detergent, Tween 80. An agarose gel with uniform pore size is used to simulate the physical barrier presented by the outer layer of skin. Apparent flexibility of the vesicles is measured indirectly via the permeation of the vesicles through a porous membrane. This talk will present results from our studies and will offer a mechanistic explanation for these results.