Pravastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor that reduces plasma cholesterol levels. Some analytical methods have been described for determination of pravastatin levels in biological fluids, but these methods are rather cumbersome and involve expensive specialized equipment, usually not available in a clinical setting. A new technique, reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection capability, has been developed for the analytical determination of pravastatin in plasma. Extraction and sample clean-up procedures are simple and rapid to execute, yet yield chromatograms virtually free of interference from endogenous plasma constituents and other antihypercholesterolemic agents or drugs usually taken concomitantly with pravastatin. Our detection limit for pravastatin was 2 ng/ml. Standard curves were linear between 5 and 200 ng/ml, with a coefficient of variation (CV) of < 10% at the limits of quantitation. This method was used to study pravastatin plasma levels in two hypercholesterolemic heart-transplant recipients and two hypercholesterolemic nontransplanted patients. We conclude that the method reported here would be ideal for therapeutic pravastatin monitoring in patients.