A high performance liquid chromatographic (HPLC) method for the determination of the anthelminthic pro-benzimidazole febantel and its major metaboites in lamb plasma has been developed. Samples were extracted after addition of albendazole as internal standard, NHOH and distilled diethyl ether. The extracted phase was dried under a stream of nitrogen redissolved in methanol and chromatographed by HPLC. Detection was by UV absorbance at 292 nm. Recovery from the plasma was 97.2, 97.1, 54.5 and 88.0% for febantel, fenbendazole, oxfendazole and oxfendazole sulphone respectively, and within-day and between-day coefficients of variation were 4.03, 4.69, 3.57 and 5.06% and 4.25, 3.73, 5.12 and 4.12%, respectively, for febantel, fenbendazole, oxfendazole and oxfendazole sulphone. The specificity and sensitivity of this method (limit of detection in plasma 0.025 μg/mL and ≤0.0125 μg/mL for febantel and its metabolites, respectively) were sufficiently high to enable us to characterize the time course of the drug in the plasma after oral administration of therapeutic doses to sheep.