The authors studied the bioavailability of minocycline in sebum and serum. Blood and sebum samples were collected weekly for 6 weeks from ten healthy volunteers taking 200 mg of minocycline every day for 4 weeks. Sebum was collected by direct extraction with petroleum ether from the forehead. After evaporation, sebum was weighed on a scale accurate to 10 micrograms. Determination of minocycline in serum and sebum was performed using a high performance liquid chromatography technique (HPLC), with a better detection limit at 352 nm than at 400 nm (20 ng/ml and 0.324 microgram/ml respectively). Our results contrast with other studies since no minocycline was detected in the sebum samples of treated subjects and microbiological assays of minocycline in sebum were also negative. In our opinion, the current hypothesis claiming that the effectiveness of minocycline in the treatment of acne vulgaris is based on sebaceous secretion should be reconsidered.