Background and Objective: Penetration of tissues by activating light ultimately limits the size of the lesions achievable in interstitial photodynamic therapy. Measurements of the wavelength-dependence of tissue optical properties suggest that substantial improvements may be possible, particularly in pigmented organs such as the liver, by using drugs absorbing at near infrared wavelengths. Study Design/Materials and Methods: In this study, the extent of light induced necrosis with the photosensitive agents Photofrin (activated at 632 nm), meta-tetra(hydroxyphenyl) chlorin (mTHPC) (activated at 652 nm) and 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) (activated at 740 nm) are compared in normal rat liver. Interstitial irradiation of mTHPBC-sensitized liver tissue resulted in significantly larger necrotic areas than irradiation of Photofrin and mTHPC-sensitised livers. Conclusion: The results illustrate the advantage of near-infrared photosensitizer activation and point to a specific role for mTHPBC in the interstitial treatment of liver tumours. Lasers Surg. Med. 27:235-240, 2000. (C) 2000 Wiley-Liss, Inc.