To investigate ketoconazole penetration into skin, a single oral dose of 200 mg was administered to six healthy subjects. Plasma and cantharides blister fluid (CBF) levels were measured for 11 to 24 hours. In suction blister fluid (SBF) ketoconazole was determined 3, 6, and 9 hours after administration. Mean peak plasma levels of ketoconazole were found at 1 hour, they amounted to 3.03 +/- 0.55 micrograms/ml (n = 5). Apparent half-life of elimination was 1.8 hours. In cantharides blister fluid maximum ketoconazole concentrations were obtained at 6 hours being 1.05 +/- 0.32 micrograms/ml and declined rather slowly (half-life 4.2 hours; n = 3). Maximum concentrations in suction blister fluid were obtained 3 hours after administration (0.914 +/- 0.123 micrograms/ml). After 9 hours ketoconazole levels had declined to 0.216 +/- 0.044 micrograms/ml (n = 3). These concentrations exceed the ketoconazole concentrations proven to be effective in vitro up to 25 fold.