Urea, 1-dodecylurea, 1,3-didodecylurea and 1,3-diphenylurea were assessed as skin penetration enhancers for the model penetrant 5-fluorouracil (5-FU). The permeability coefficient ( K p) was determined for 5-FU applied in saturated aqueous solutions to human epidermal membranes. Then each urea was applied as a saturated solution m dimethylisosorbide, light liquid paraffin or propylene glycol: the solutions were removed and K p was redetermined; the enhancement ratio ( K p after enhancer treatment/ K p before enhancer treatment) measured the accelerant effect. Urea and the vehicles alone were ineffective as enhancers; the urea analogues behaved similarly at saturation in any one vehicle; and the analogues were only effective when delivered from propylene glycol, enhancing the permeation of 5-FU 6 times by increasing the diffusivity of the stratum corneum. Thus, the role of propylene glycol as a synergistic vehicle for penetration enhancers was confirmed.