Hematoporphyrin derivative phototherapy (HpD-PT) is currently being used experimentally in the treatment of various malignancies. The effectiveness of HpD-PT appears to be limited to superficial malignancies because of its inability to penetrate more than 0.5-1 cm. The mechanism of action has been demonstrated to result from the formation of toxic singlet oxygen and other oxygen radicals. Preliminary work suggested that the addition of other chemical agents known to produce toxic oxygen radicals may enhance the effect of HpD-PT. To test this hypothesis, we examined the effectiveness of HpD-PT in the Walker 256 carcinosarcoma with and without Adriamycin. Tumor kill was estimated by calculating the area of necrosis on photomicrographic sections. From this area, a radius of tumor necrosis was determined and compared among various control and experimental groups. HpD-PT was effective in this model when compared to control groups (radius of necrosis 3.79 f 0.97 mm vs. 2.60 f 1.26 mm, P < .05). The addition of Adriamycin significantly increased the radius of necrosis when compared to HpD-PT (4.57 f 1.70 mm vs. 3.69 f 0.97 mm, P c .01). From this work we conclude that HpD-FT demonstrates effective tumor killing in this murine model. The addition of Adriamycin significantly increased tumor kill.