Leflunomide (Arava), a drug with immunosuppressive and antiviral effects, is being used in renal transplant recipients, primarily for its action against BK polyomavirus (BKV), which affects 1% to 10% of renal transplant recipients and often causes failure of grafted kidneys. Leflunomide effects are solely due to an active metabolite, teriflunomide (formerly A77 1726). Trough blood concentrations of teriflunomide exceeding 40 microg/mL (148 micromol/L) are associated with progressive clearance of BKV. Toxic effects become increasingly apparent at higher concentrations. We have developed a rapid, simple, and robust high-performance liquid chromatography (HPLC) method for therapeutic monitoring of teriflunomide in renal transplant recipients. Sample preparation is rapid, and each HPLC separation takes about 7 minutes. Intraday and interday coefficients of variation were 1.5% or less and 5.6% or less, respectively. The method was linear to 200 microg/mL (740 micromol/L), which is well above teriflunomide concentrations that are likely to be observed.