Photodynamic therapy (PDT) involves the parenteral administration of a photosensitising agent with some selectivity for malignant tissue. When activated by light, usually from a laser, local tissue destruction occurs. The amount of tissue destruction is dependent on the concentration of the photosensitising agent in the tissue and the light energy delivered. By careful manipulation of laser energy and photosensitiser dosage true selective destruction of malignant tissue can be produced in experimental colon cancers with total sparing of normal colon although under these conditions, the extent of necrosis in the tumour is only 2-3 mm from the light source. In addition, PDT has been shown not to reduce the mechanical strength of the colon even if full thickness necrosis is produced in normal areas. In contrast, thermal full thickness laser damage of the colon considerably weakens the colonic wall and may cause perforation. Light microscopy with specific collagen stains and electron microscopy have shown that the submucosal collagen layer is preserved following PDT, but is destroyed by thermal laser therapy. An initial clinical trial of PDT has been performed in ten patients with inoperable tumours because of advanced metastatic disease or severe medical problems. PDT has been shown to be safe and some small colorectal cancers can be totally eradicated.