Within 3 h of intra-ruminal (IR) administration oxfendazole (OFZ) was extensively associated with digesta particulate material. This association appeared to be a passive adsorption/desorption since sheep given dose equivalent OFZ which was contained solely in rumen particulate digesta (obtained from OFZ treated donor sheep) exhibited similar OFZ disposition to the IR treated animals. The association of OFZ with rumen particulate digesta is a major determinant of the pharmacokinetic behaviour of OFZ. The kinetic disposition of OFZ was compared in sheep fed 400 g and 800 g day-1 of 50:50 lucerne/wheaten chaff. The flow rate of rumen and abomasal fluid and particulate digesta increased with feed intake whilst the availability of OFZ and its metabolites in the digestive tract and bloodstream decreased. Compared to untreated sheep fed 800 g day-1, OFZ did not affect benzimidazole (BZ) resistant Trichostrongylus colubriformis, but reduced the numbers of BZ-resistant Haemonchus contortus by 61%. When sheep were fed 400 g day-1 36 h before and after OFZ administration, 60% of T. colubriformis and 94% of H. contortus were removed. Elevated anthelmintic efficacy in sheep can therefore be obtained when gastric flow has been slowed by temporarily reducing feed intake.