Plasmid DNA is efficiently photocleaved by sodium pheophorbides (Na–Phdes) a and b in the absence of oxygen as well as in the presence of oxygen. Fluorescence microscopic observation shows a rapid incorporation of Na–Phde a into nuclei, mitochondria, and lysosome of human oral mucosa cells. In contrast Na–Phde b is incorporated only into the plasma membrane. The photodynamic activity of these pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures and involves two types of reactions: (i) direct electron transfer between DNA bases (especially guanine) and pheophorbide singlet excited state, and (ii) indirect reactions mediated by reactive oxygen species, including singlet oxygen whose production from molecular oxygen is sensitized by the Na–Phdes triplet state. A preliminary report has appeared in ‘‘Photodynamic Therapy of Cancer II,’’ Proc. SPIE 2325, 416–424 (1994).