We conducted a trial of photoradiation therapy of cancer at the University of California at Irvine. The basis of this technique is a photochemical reaction between an i.v.-injected material, hematoporphyrin derivative, and red light (wavelength, 630 nm). Hematoporphyrin derivative localized in malignant tissue, resulting in selective destruction of cancer cells upon illumination with red light. One hundred twenty-eight sites of recurrent cancer or premalignant lesions were treated in 37 patients. Of this group, 35 patients had recurrent cancer refractory to conventional therapy, and two had premalignant lesions. Favorable responses were achieved in 67% of the sites treated. The dose of hematoporphyrin derivative used in this study ranged from 2 to 5 mg/kg with the majority of patients receiving 3 mg/kg. Total light dose administered appeared to be the most critical parameter evaluated. Light doses in excess of 20 J/sq cm generally resulted in blistering and necrosis of intact skin, while no appreciable increase in response was observed. Photoradiation therapy has demonstrable efficacy in cancer therapy and avoids much of the morbidity of current conventional techniques.