Absolute concentrations in the horny layer, epidermis, and dermis of therapeutical doses of topically applied hydrocortisone to human skin (in vivo) are reported. Using vaseline as vehicle 2-10(-4) molar concentrations are found in the epidermis and 3-10(-5) molar concentrations in the dermis. Further, three vehicles revealed minor concentrations. Comparison of the results with similar in vitro-investigations, reported earlier, allow to judge the resorption rate by the intact capillary system. Uptake of hydrocortisone by the vessels is observed. With high rates of penetration vasoconstriction seems to limit the resorption, while this is not the case with low rates, for instance with polyethyleneglycol as vehicle. Thus a differing drug liberation from the vehicle causes qualitatively different permeation kinetics. The elimination by urine, however, was practically the same. It is concluded that different vehicles may cause different therapeutic concentrations of the drug in the skin, but equal systemic side effects.