Moxidectin is a newly developed potent anthelmintic agent with a high potency although present at very low concentration in cattle plasma. A method is described for the determination of moxidectin in plasma using high-performance liquid chromatography with fluorescence detection (excitation and emission wavelengths 383 and 447 nm, respectively). The fluorescent derivative was obtained by a dehydrative reaction with trifluoroacetic anhydride and N-methylimidazole. The method employs 1-ml plasma samples and has linear calibration graphs (r = 0.997) over the concentration range studied, i.e., 0.1-10 ng/ml. Solid-phase extraction using the Benchmate procedure was used for sample preparation. Recoveries at low concentrations (0.1-10 ng/ml) were higher than 75%. The limit of quantification was 0.1 ng/ml (C.V. 6.95%). The method is suitable for the pharmacokinetic study of moxidectin after subcutaneous administration to cows.