For soft tissue sarcomas with high local recurrence rates following seemingly adequate surgical excision, intraoperative photodynamic therapy (IOPDT) provides a treatment strategy to eradicate microscopic, residual disease. Six Fischer 344 rats were given bilateral subcutaneous syngeneic 9L gliosarcoma tumors. When tumors reached 1.0 cm3, the rats were given 200 mg/kg ALA by intraperitoneal injection. Four hours later the rats were anesthetized, both tumors were incompletely excised and one surgical field was treated with 635 nm laser light (75 mW/cm2, 100 J/cm2). The surgical sites were then closed and the rats were monitored for local recurrence of the tumor. Low intensity fluorescent microscopic images captured with a cooled CCD camera confirmed that the tumors converted ALA into PpIX. Post-IOPDT swelling of the treated leg lasted 48 hours. An 80% local recurrence rate was observed in both groups 14 days following treatment. There was no difference in wound healing between IOPDT-treated sites and sites treated with surgery alone. Recurrent tumors were smaller in IOPDT sites than those treated with surgery alone. Additionally, the IOPDT recurrences were at the margin of the treatment field, suggesting a photoirradiation 'geographical miss.' These preliminary results, although disappointing, suggest that with further refinement IOPDT is a promising treatment modality for traditionally difficult to treat tumors.