In recent years, chloroaluminum phthalocyanine tetrasulfonate (AlPCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, AlPCTS is going to be under clinical trials of PDT. In this study, in vitro addition of AlPCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (∼675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of AlPCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, β-carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the AlPCTS-mediated photodestructive process. © 1990 Academic Press, Inc.