Dilution of semisolid preparations, in order to tailor the formulations to the needs of the patients, was thought to be associated with a number of dangers, one of which is the unpredictable alteration of activity. In the present study the influence of dilution on hydrocortisone permeation through excised human stratum corneum was investigated. The permeation profiles of hydrocortisone from various cream bases (diluted and undiluted) were found to be very similar with no significant differences. This result was in accordance with the lack of interaction between the tested bases and the structure of stratum corneum as shown by differential scanning calorimetry experiments. Thus, the permeability of stratum corneum, which was not affected by the cream bases, is the rate limiting step for drug permeation. However, it could be shown that dilution of Soventol cream (placebo with 1% hydrocortisone) which is known to contain isopropyl myristate as permeation enhancer reduces drug permeation. The reduced hydrocortisone permeation is believed to be due to reduced enhancer concentration.