A toxicity study was performed in a canine model to explore the feasibility of using intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis. Dogs received 1.25 mg/kg Photofrin II both intravenously (48 hours) and intraperitoneally (2 hours) before intraperitoneal light treatment. The entire peritoneal surface was illuminated with 0.57-0.74 J/cm2 of red light (630 nm). Thirteen dogs were treated: 4 control and 9 full treatment. Of the fully treated dogs, 5 received a single treatment and 4 received 3 treatments. The dogs were evaluated clinically and pathologically for immediate (4 days) and late (60 days) side effects. All animals tolerated the treatment without significant morbidity. Postoperative blood tests were normal except for low lymphocyte counts and elevated liver transaminases, both of which normalized rapidly. Histopathologically, there was approximately a 50% incidence of mild inflammatory peritoneal response. This study provides the basis for a Phase I human trial.