The biotransformation of 3H labelled butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit, FCB) was examined in vivo in the intact and pre-damaged skin of guinea pigs and in vitro in excised skin from guinea pig and humans. The active ingredient was applied as 0.75% W/O-emulsion. At the end of the period of exposure the substance remaining on the skin was recovered with the aid of cotton wads or Tesa adhesive tape and the spectrum of metabolites in the skin and the rinsing fluid determined by thin-layer chromatography. FCB is only slowly degraded in the skin of guinea pigs and humans to produce its main metabolites 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadiene-21-acid and its derivative by decarboxylation 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-androstadiene-17beta-carboxylic acid. 4 h after application 80--85% unaltered active principle was still identifiable in the intac skin and approximately 70% in the damaged skin of the guinea pig. In the human skin the amount was approximately 90% 7 h after application. The amount of active ingredient in the perfusion medium was about 65% while the amount of steroid acids was about 25%. Despite the extremely low rate of absorption the slow ester hydrolysis of FCB in human skin results in a persistent, high level of active ingredient in the skin.