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1. The fate of dietary histamine in sheep has been studied. When 200 mg histamine diphosphate was administered into a rumen with normal contents the average time taken for the biological activity to disappear from the rumen was about 4 hr. In sheep starved for 60 hr the activity disappeared much more slowly.

2. When 0·9% NaCl solution was substituted for the normal rumen contents and the rumen was isolated in situ under anaesthesia, the disappearance of histamine was scarcely detectable. About 1% of the radioactivity introduced into such rumen preparations as [¹⁴C]histamine was recovered in the urine during a 6 hr period.

3. When both [¹⁴C]histamine and 200 mg unlabelled histamine diphosphate were administered into the rumen, between 4 and 15% of the radioactivity and 2 and 11% of the biological activity reached the duodenum.

4. When jejunal loops isolated between two pairs of re-entrant cannulas were perfused with 0·9% NaCl solution containing histamine a considerable fraction of the histamine was absorbed from the loops.

5. When [¹⁴C]histamine and 200 mg histamine diphosphate were administered into the rumen an average of 9% of the radioactivity appeared in the urine. When histamine was given into the abomasum the corresponding figure in a single experiment was 25%.

6. Between 11 and 34% of the radioactivity administered into the rumen as [¹⁴C]histamine was exhaled as ¹⁴CO₂. Most of the ¹⁴CO₂ seemed to stem from metabolism of [¹⁴C]histamine in the ruminoreticulum whereas the contribution of the intestines to ¹⁴CO₂ was very small.

7. When [³H]histamine was administered into the rumen most of the radioactivity in the urine a few days after administration was in the form of tritiated water. The formation of ³H₂O is probably a result of histamine metabolism in the fore-stomach, analogous to the formation of ¹⁴CO₂.