The influence of molecular oxygen and oxygen radicals on the photoreactivity of the antimalarial drug primaquine (PQ) has been investigated. Oxygen is directly involved in photodecomposition of the drug. Flushing with helium gas prior to and during irradiation to suppress the oxygen level of the medium, retards the degradation rate of PQ (followed by HPLC) and leads to the formation of only two degradation products (identified by MS) compared to eight main- and several minor products under normal atmospheric conditions. Flushing with oxygen gas prior to and during irradiation to increase the oxygen content of the medium accelerates the degradation rate of PQ. PQ produces oxygen radicals (hydroxyl and superoxide) during photolysis, while the photoproducts of PQ seem likely to induce singlet oxygen formation (detected by addition of radical scavengers). Sensitization reactions involving singlet oxygen lead to decomposition of PQ (followed by HPLC). On the basis of our results, photochemical reaction mechanisms of PQ are postulated and discussed. At physiological conditions (aqueous, neutral pH, oxygen rich) PQ has a large potential to decompose after light absorption. The photoreaction seems to be initiated at the quinoline nitrogen. The ability to form an intramolecular hydrogen bond seems to be essential for the luminescence properties of the drug. Phosphorescence lifetime of PQ is about 5 microseconds. Fast chemical reactions may occur from the short-lived triplet state of the drug, but the excited compound can diffuse only a limited distance prior to deexcitation. This can be important concerning light-induced adverse effects which may appear after medication with PQ.