The dense lipid bilayers at the outer surface of the skin represent the primary barrier to molecules penetrating the human skin. One approach to overcome this barrier, with promising applications in administering medicinal drugs to the body, is to employ chemical permeability enhancers. How these enhancers, such as dimethylsulfoxide (DMSO), exert their effect at the molecular level is only partly understood. We present molecular dynamics simulations to elucidate the interaction of DMSO with bilayers of ceramide 2, the most abundant lipid in the skin. The DMSO molecules are found to weaken the impermeable crystalline bilayers, and even to cause a transition to a fluidized phase at high DMSO concentrations. This is consistent with the experimental evidence that a substantial concentration of DMSO is required to enhance the permeability of the skin. Trans-membrane pores are created using a constraint technique, and the free energy change during pore formation is calculated. High DMSO concentrations yield archetypal hydrophilic pores, i.e. the membrane edge surrounding the pore is lined with lipid head groups, while in pure water we observe the formation of hydrophobic pores, i.e. the lipid tails are exposed at the membrane edge. Although hydrophobic pores are commonly envisaged to contain water, we find that nanometer-sized pores are actually empty. The origins and consequences of these vapour pores are discussed.