5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (Pp IX), was administered into the rat uterine cavity in an attempt to selectively ablate the endometrium. Doses of ALA ranging from 4 to 50 mg were injected into one uterine horn of rats while the vehicle (saline) was injected into the contralateral horn. Animals were divided into three groups. In group one, the uterine horns were removed and processed for either fluorescent microscopy or spectrophotofluorometry 3 h later. In group two, rats were allowed to survive for either 2 or 10 days, and then the uterine horns were harvested and processed histologically. In group three, both uterine horns were exposed to transmural light (approximately 150 J/cm2) 3 h after administration of ALA or saline and processed histologically either 2 or 10 days later. Fluorescent microscopy showed fluorescence in the endometrium and not in the myometrium. The maximum emission spectra of endometrial fluorescence occurred at 630 and 690 nm, characteristic of Pp IX. In contrast, no fluorescence was detected in saline-treated uterine horns. Light exposure resulted in extensive damage only to the ALA-treated endometrium. There was no indication of regeneration 10 days after treatment. We conclude from these studies that ALA administered into the lumen of the rat uterus is selectively converted into Pp IX within the endometrium. Furthermore, photoactivation of the Pp IX results in selective ablation of the endometrium.