Laser targeted photo-occlusion (LTO) is a novel method being developed to treat choroidal neovascular membranes (CNV) in age-related and other macular degenerations. A photosensitive agent, encapsulated in heat-sensitive liposomes, is administered intravenously. A low power laser warms the targeted tissue and releases a bolus of photosensitizer. The photosensitizer is activated after it clears from the normal choriocapillaris but not from the CNV. Forty-five experimental CNV were induced in seven rats. Five weeks after LTO, complete occlusion was observed by laser targeted angiography (LTA) in 76% of treated CNV, and partial occlusion was found in the remaining 24%. The tissues outside the CNV but within the area treated by LTO showed no flow alteration and no dye leakage. All untreated CNV were patent on LTA at 5 weeks. Light microscopy and electron microscopy confirmed the results in treated and control lesions. Moreover, treated areas next to lesions showed normal photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris. These results indicate that LTO may improve current photodynamic therapy by alleviating the need for repeated treatments and by avoiding the long-term risks associated with damage to the RPE and occlusion of normal choriocapillaries.