The tumoricidal effect of the activation of hematoporphyrin derivative (HpD), by an argon-ion-dye-laser (wavelength 630 nm), was investigated in the Buffalo rat bearing subcutaneous implants of the Morris 7777 hepatoma. Tumor growth was monitored by measuring the tumor volume with constant force callipers. In control animals and those that were pretreated with HpD alone (10 or 20 mg per kg by i.p. injection) or laser light alone (2,000 J at 100 mW), a predictable exponential growth pattern of the cancer was observed. Animals were pretreated with HpD (10 mg per kg by i.p. injection) 48 hr prior to the fiberoptic, intratumor delivery of laser radiation (2,000 J at 100 mW), when the tumor had reached a volume greater than 1.5 cm3. Forty-eight hours after combined laser and HpD treatment, the hepatoma underwent coagulation necrosis, and the tumor volume rapidly increased from a mean value of 1.8 ± 0.7 cm3 S.D. to a value of 5.8 ± 1.5 cm3 S.D., compared with a mean of 3.7 ± 0.7 cm3 S.D. in animals who had not received laser phototherapy. Rats treated with HpD and laser light survived longer (mean survival time 48 ± 12 days S.D.) than did the other animals treated with the laser alone or HpD alone (mean survival time 31 S± 16.5 S.D.). Tissue biodistribution studies with tritiated hematoporphyrin derivative, given with doses of 10 and 20 mg per kg of HpD, showed higher concentrations of the dye in the liver, kidneys and spleen than in the tumor at 48 hr after administration of the dye. The ratio of uptake of HpD between the Morris 7777 hepatoma and adjacent muscle was approximately 2:1 in both dose ranges of the dye, implying that HpD does not localize in malignant tissue in a preferential manner. Laser phototherapy with HpD significantly interrupts the growth of the highly malignant Morris 7777 hepatoma and prolongs the survival time of Buffalo rats bearing this neoplasm.