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Sheep were ‘compartmentalized’ by surgically implanting cannulae in the rumen, abomasum and terminal ileum with a re‐entrant cannula inserted between the cystic duct and the duodenum to monitor bile secretion. Doramectin, containing a trace of [³H]‐doramectin, was administered both intravenously (i.v.) and intraruminally (i.r.) at a dosage of 150 μg/kg. The pharmacokinetic behaviour of [³H]‐labelled products was determined in these pools, and also in peripheral plasma, urine and faeces. Parent doramectin was also determined in plasma, abomasal digesta fluid and bile. Following i.r. administration, [³H] compounds were almost entirely associated with particulate digesta. A 14.5‐h half‐life in the rumen prolonged the presence of [³H] in the abomasum. Doramectin appeared to be degraded in abomasal digesta because only 24% of abomasal [³H] was attributed to the parent drug. Absorption of doramectin …