The effect of photodynamic therapy (PDT) with a hematoporphyrin derivative (HPD) on tumor cell survival was studied in 9L gliosarcoma rat tumor systems, both in vitro and in vivo. In vitro, the cytocidal effect was dependent on HPD concentration and length of exposure to light. The cell death rate was 100% with 30 minutes of light exposure following 6 hours of culturing in a medium containing 50 μg/ml of HPD. Male Fischer 344 rats were inoculated with 9L gliosarcoma cells to produce frontoparietal surface brain tumors. An argon laser with a wave length of 514.5 nm was used as the light source. The rats were divided into several groups and received either no treatment (controls) or one of various combinations of treatment: HPD without light irradiation, placebo plus light irradiation, or HPD plus light irradiation. No degenerative changes were observed histopathologically in the control rats or those not given HPD. Necrotic foci were prominent in the groups given HPD, regardless of whether the light was delivered directly to the tumor surface or to the skin just above the tumor. The necrotic change of the tumor cells comprised nuclear pyknosis, homogenation of chromatin, and vascular collapse associated with extravasation, venous congestion, hyalinization of endothelium, and massive hemorrhage. These results demonstrate the cytocidal effect of PDT on experimental glioma and suggest that this approach will have important clinical application in neurooncology.