Abstract—–Photohemolysis of erythrocytes. from patients with erythropoietic protoporphyria results from damage to the cell membrane following photoexcitation of the protoporphyrin molecule by 400 nm radiation. Photochemical reactions were assessed for their roles in initiating cell destruction in anin vitromodel in which erythrocytes from patients with erythropoietic protoporphyria were irradiated. Electron transfer properties were demonstrated using 2,3,6‐trichloroindophenol as an electron acceptor. Photohemolysis of these abnormal cells is due to cell membrane damage initiating colloid osmotic hemolysis. Additional data are offered demonstrating that this type of photohemolysis is oxygen‐dependent, associated with peroxide formation, and preceded by increased osmotic fragility. An hypothesis explaining the interrelationship of the photochemistry of protoporphyrin with the photobiologic observation of hemolysis is