We have previously established that the relative concentrations of propylene glycol and ethanol as a binary solvent system have a significant effect on the skin penetration of 2% solutions of minoxidil at 50 microL/cm2. The present work extends these studies and investigates the penetration of minoxidil from the different vehicle combinations as functions of application volume and occlusion. Decreasing the application volume has a variable effect which depends on vehicle composition. Penetration of minoxidil from 100% ethanol solutions decreased linearly with application volume. Generally, irrespective of the volume applied, the penetration of minoxidil increased with increasing ethanol fraction with a maximum penetration at 90% ethanol. Penetration from all the formulations was enhanced upon occluding the skin, with greatest increase evident in solutions with higher volatile fraction. Penetration of minoxidil in vivo showed trends similar to those seen in vitro.