The phthalocyanines are a new class of photosensitizers with promising properties for use in photodynamic therapy of cancer [E. Ben-Hur and I. Rosenthal (1985) Int. J. Radiat. Biol., 47, 145--147]. The ability of aluminum phthalocyanine tetrasulfonate (AlPCS) to cause membrane damage upon light exposure was tested using photohemolysis of human erythrocytes as an endpoint. AlPCS was found to be quite efficient in causing red blood cell lysis. Photohemolysis dependency on the light fluence had a characteristic sigmoidal shape. The light fluence required for 50% hemolysis was inversely proportional to AlPCS concentration. Neither singlet oxygen nor hydroxyl radicals appear to be involved in the photohemolysis induced by AlPCS. This is inferred from the observation that exposure of erythrocytes in the presence of D2O or glycerol did not affect the light fluence response curve. These data suggest that photosensitization by AlPCS can cause membrane damage and that this damage may be responsible for cell killing.