The bioavailability of carbazeran and the metabolism of carbon-14 labelled drug have been studied in the dog and man following oral administration. The drug was moderately well absorbed in both species, but there was a marked difference in bioavailability and in routes of metabolism. In the dog, systemic bioavailability was approx. 68% and biotransformation involved mainly O-demethylation. In man, bioavailability was not measurable and carbazeran was almost completely cleared via 4-hydroxylation of the phthalazine moiety. Thus the lack of detectable pharmacological effect in man following oral administration of the drug appears to be due to presystemic metabolism by a particularly active pathway not found in the dog.