Sulfonated tetraphenyl porphines (TPPS, ) are photosensitizing dyes that localize in lysosomes of NHIK 3025 cells. In order to elucidate the mechanisms of cell inactivation by photochemical treatment with TPPS,, lysosomal enzyme inactivation and release of Iysosomal contents were examined after treatment. In cells treated with TPPS4 and light, the lysosomal enzymes P-N-acetyl-D-glucosaminidase (fl-AGA) and cathepsin(L + 6 ) were almost completely inactivated and no enzyme activities were released from the lysosomes. In contrast, a maximum of 30 and 50% of the initial P-AGA activity was released from lysosomes after treatment with TPPS, and TPPSa, respectively. Forty per cent of the initial P-AGA activity was released after treatment with TPPSk and a non-cytotoxic dose of light. After such a treatment only approximately I W o of the initial cathepsin activity was found in the cytosol fraction and in all other cases no cathepsin activity was recovered in the cytosol fraction after photochemical treatment. It was found that the constituents of the cytosol partly inhibited cathepsin activity. This inhibitory effect was not influenced by the photochemical treatment, neither was the colony-formingability of photochemically treated cells influenced by pre-treatment with the cathepsin inhibitor EM. The present results indicate that NHlK 3025