1. Oxidative degradation of the pentyl side-chain of cannabinoids leading to compounds containing even numbers of carbon atoms was studied by investigating the in vivo metabolism of 2'- and 3'-hydroxy-delta-9-tetrahydrocannabinol (THC). 2. The hydroxy cannabinoids were administered i.p. to mice, the livers were removed after 1 h and extracted metabolites were identified by g.l.c.-mass spectrometry. 3. The major metabolic route for both compounds was hydroxylation at the allylic 11-position followed by oxidation to a carboxylic acid. Additional hydroxylation occurred at C-8. 4. Little oxidative degradation of the side-chain was found for 2'-hydroxy-delta-9-THC but abundant metabolites were formed by this route from the 3'-hydroxy compound. 5. The major metabolites of this type were acids containing three carbon atoms in the chain. These are the normal products of beta-oxidation but their formation from an (omega-2)-hydroxy intermediate appears novel. 6. Other metabolites contained two carbon atoms in the side-chain but were alcohols rather than acids and were again apparently formed by novel mechanisms. 7. The results indicate that the major route leading to cannabinoid metabolites with two-carbon side-chains (loss of three carbon atoms) is initiated by omega-2 hydroxylation.