A sensitive and selective liquid chromatographic tandem mass spectrometric (LC-MS-MS) method for analysis of lovastatin in human plasma has been developed and validated. Ethyl acetate extraction was used for plasma sample preparation and simvastatin was used as internal standard. Chromatographic separation was achieved on a C18 column by isocratic elution with 83:17:0.1 (v/v) methanol-2 μM aqueous sodium acetate-formic acid as mobile phase, delivered at 1.0 mL min−1. MS-MS detection was performed using positive electrospray ionization and multiple-reaction monitoring with argon for collision-induced dissociation. Calibration plots were generated over the concentration range 0.05 to 20 ng mL−1 (r > 0.999) with a lower limit of quantification (LLOQ) of 0.05 ng mL−1. Intra and inter-day precision and accuracy were determined at four different concentrations, 0.05, 0.5, 2.0, and 10.0 ng mL−1, and precision ranged from 0.4 to 11.4% with the deviation always less than 15% (n = 5). Extraction recoveries were from 86.8 to 94.1% for lovastatin and approximately 88.0% for simvastatin. The validated method was successfully applied to a bioequivalence study of two lovastatin tablets in 20 healthy volunteers.