The autoxidation of tetrahydrofolic acid and tetrahydrobiopterin, 6-substituted derivatives of 2-amino-4-hydroxy-5,6,7,8-tetrahydropteridines (tetrahydropterins), has been investigated by product analysis and kinetic methods. The overall reaction is first order in tetrahydropterin and approximately first order in oxygen, with an activation energy of 58 kJ mol–1. There is a linear dependence of rate on the percentage ionisation of the 3,4-amide group. Kinetic data are in accord with a free radical chain reaction in which the chain carrier is the hydroperoxyl radical (HO2·), not alkylperoxyl radical, and propagation is accompanied by formation of a transient quinonoid dihydropterin intermediate, rearrangement of which results in the formation of the products described. Oxygen-18 labelling experiments show that the autoxidative ring contraction of 1,3,6,7,8-pentamethyl-5,6,7,8-tetrahydro-pteri-2,4-dione does not provide evidence for the intermediacy of 8a-hydroperoxides during the reaction.