NADPH reacts efficiently with singlet oxygen (1O2), the predominant oxidation product being enzymatically active NADP. This reaction acting in concert with the cytoplasmic NADPH regenerating enzymes may contribute to the protection of cytoplasmic components against (1O2) mediated toxicity. NADP-linked isocitrate dehydrogenase [pig heart, EC 1.1.1.42] is inactivated by (1O2) photochemically generated with hematoporphyrin. When NADPH is present during photooxidation, the enzyme is protected from complete inactivation and regenerates the factor (NADPH) responsible for its own protection.