OBJECTIVE:Our purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid. STUDY DESIGN:Three hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber. RESULTS:A 64 J/cm2 in situ optical dose resulted in long-term irreversible endometrial destruction; 43 J/cm2 damaged endometrial stroma and myometrium but not glandular epithelium 1 day after photodynamic therapy. At this lower light dose endometrium regenerated to full thickness within 3 weeks; however, implantation sacs were significantly reduced. CONCLUSIONS:Photodynamic destruction of glandular epithelium accompanies irreversible endometrial ablation, whereas isolated stromal damage leads to reproductive impairment only. The optical dose required for endometrial ablation is approximately 1.5-fold higher than for reproductive impairment (functional damage) because of differential cell photosensitivity.