In preliminary studies, the efficacy of a new photosensitizer, pyropheophorbide-(alpha) - hexyl ether (HPPH #23), for use in photodynamic therapy (PDT) was assessed using the rat 9L gliosarcoma tumor model in subcutaneous flank tumors, intracranial tumors, and in vivo. Flank and intracranial tumors were irradiated with 75 - 203 J/cm2 24 hours after 0.3 - 0.6 mg/kg IV injection of HPPH #23. At 24 hours post-PDT, and flank tumors showed a range of necrosis at the highest laser dose from 50 - 100%. The overlying skin and underlying muscle were spared. Intracranial tumors exhibited moderate to severe hemorrhagic necrosis. Areas of brain adjacent to tumor within the irradiated field also showed some damage. In vitro phototoxicity of HPPH #23 was compared to that of Photofrin II (PhII). Cells growing in culture dishes were exposed to HPPH #23 or PhII for 20 hours, washed free of unbound drug, then irradiated at 2.5 J/cm2, 17 mW/cm2 at 665 nm (HPPH #23) or 630 nm (PhII). Irradiated cultures were maintained in dark incubators for an additional 4 - 5 days, and phototoxic inhibition of cell proliferation was quantified by the sulphorhodamine B spectrophotometric assay. Under identical irradiation conditions, the IC50 for HPPH #23 (0.25 (mu) g/ml) was 10-fold lower than that of PhII (2.5 (mu) g/ml). Complete cell kill was achieved at sensitizer doses of 0.5 (mu) g/ml (HPPH #23) and 5.0 (mu) g/ml (PhII).