Results of in vitro studies on the penetration of a corticosteroid hydrocortisone 17-butyrate (HCB) in relation to the vehicle are reported. When HCB is dissolved completely in the vehicle, penetration is enhanced, and only under this condition an increase in HCB concentration (in the range 0.05–0.2%) leads to an increase in the penetration. Evaluation of the efficiency of various vehicles (an oil/water cream, Plastibase® or gels) in which HCB was dissolved in propylene glycol or ethanol, showed that Plastibase with propylene glycol was the most effective for both 0.1 and 0.2% HCB. The results of experiments in which HCB was applied in ethanolic solutions suggests that at least initially HCB and ethanol together penetrate through the epiderm