A sensitive and specific high-performance liquid chromatographic (HPLC) method with UV detection was developed for the determination of minocycline in human plasma and parotid saliva samples. Samples were extracted using an OasisE HLB cartridge and were injected into a C Nucleosil column. The HPLC eluent contained acetonitrile-methanol-distilled 8 water-0.1% trifluoroacetic acid (25:2:72.9:0.1, v / v). Demeclocycline was used as internal standard. The assay showed linearity in the tested range of 0.1-25 mg / ml. The limit of quantitation was 100 ng / ml. Recovery from plasma or parotid saliva averaged 95%. Precision expressed as %CV was in the range 0.2-17% (limit of quantitation). Accuracy ranged from 93 to 111%. In the two matrices studied at 20 and 48C, rapid degradation of the drug occurred. Frozen at 2308C, this drug was stable for at least 2 months, the percent recovery averaged 90%. The method's ability to quantify minocycline with precision, accuracy and sensitivity makes it useful in pharmacokinetic studies.