1. The elimination of immunoreactive secretin was studied in anaesthetized pigs by using constant infusions of pure natural porcine secretin.
2. The mean metabolic clearance rate was 15·4 ml min—1 kg—1, and was independent of the level at which it was determined. The mean distribution space was 64·4 ml/kg. The half-life of secretin after termination of the infusion averaged 2·6 min.
3. During intravenous infusion of secretin in a dose of 27·8 pmol h—1 kg—1 the renal extraction was 52%. Exclusion of the kidneys increased plasma secretin concentration from 26·5 pmol/l to 47·3 pmol/l and increased the half-life to 4·4 min.
4. Exclusion of the liver during infusion of secretin in a dose of 27·8 pmol h—1 kg—1 resulted in an increment in plasma secretin concentration of 7·8 pmol/l and an increase of the half-life to 3·6 min.
5. A gradient of endogenous secretin across the liver was present but no arteriovenous difference was found across the foreleg.
6. Incubation of secretin with whole blood or serum for 20 min at 37°C did not result in any degradation of secretin.