The use of hematoporphyrin derivative and other photosensitizing agents in combination with light activation is currently being investigated as an anti-tumor modality for the treatment of intraperitoneal and intrathoracic tumors. A major advantage of this modality is the apparent selective retention of the sensitizing dye within tumors. A murine ascites ovarian carcinoma and a human ovarian tumor have been used to study the characteristics of drug distribution in the peritoneal cavity. Initially, murine models were used to study the tolerance of the thoracic cavity structures to the phototherapy techniques being explored. The limitations of the murine model has required the extensions of the investigation to the canine model for evaluation of the toxicity of Phototherapy. Different wavelengths of light, different laser delivery systems, different sensitizers, different doses of energy, different modes of drug administration, and different monitoring devices were studied. We have shown that Phototherapy can be used to effectively treat a murine ascites tumor. We have also shown that in both the murine and the canine model, the peritoneal serosal surface is tolerant of at least 0.5 J/cm2 and that this work can be extended to human subjects. In the murine system, we have shown that the thoracic cavity, like the peritoneal cavity, is exquisitely sensitive to treatment with red light (630 nm). The dose rate must be controlled to minimize heat buildup (less than 150 mW fiber output from a forward projecting optical fiber is usually tolerated). We have extended a toxicity study to the canine thoracic cavity and shown that structures such as the esophagus, parietal and visceral pleura, heart can tolerate 35 J/cm2 red light. Currently, there is an ongoing Phase I trial using DHE/630nm light to treat unresectal mesothelioma. Currently, 32.5J/cm has been used in the clinical treatment of mesothelioma. We are exploring the use of photoimmunotherapy as an additional means of drug delivery. An athymic murine model transplanted with human lung cancer was used to study photoimmunotherapy. Hematoporphrin was covalently bound to the specific monoclonal antibody directed against the xenograft. The results show that tumor can be eradicated and that dermatophotoxicity is eliminated. We are exploring the use of chemiluminescence as a means of light delivery to the cavitary spaces. A new class of water soluble agents arc being used. New forms of energy delivery for activation of sensitizer are being explored.