Over recent years there has been a resurgence in the use of doxycycline in clinical practice, which does not depend on its antibacterial properties. This paper describes a method of determination of doxycycline in human plasma and atheromatous tissue using high-performance liquid chromatography (HPLC), and a cheap commercially available extraction system. Doxycycline is extracted in the mobile phase and injected directly into the HPLC system, avoiding time consuming drying up steps. A limit of detection of 0.125 microg/ml of plasma, and a relative standard deviation of 3% was achieved, making the method very reliable and useful for assays within the usual therapeutic range. The method has also been applied to the extraction of a mixture of tetracyclines from plasma and atherma with equal efficacy, making it useful for assays of this class of drugs in veterinary practice and assays of food contaminants.