Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent. We performed a study of topically applied 5-aminolevulinic acid (5-ALA) in the photodynamic treatment of women with high-grade cervical intraepithelial neoplasia (CIN) using fixed 5-ALA doses and application protocols derived from previous in vitro and in vivo results. Three to 5 hr prior to PDT, 10 ml of a 20% solution of 5-ALA was topically applied using a cervical cap. PDT was performed with irradiation of 100 J/cm2 at an irradiance of 100-150 mW/cm2 with an argon-ion-pumped dye laser at 635 nm. For the endocervix, a specifically designed cylindrical applicator was used. Ten treatment cycles of PDT using 5-ALA were performed in 7 patients with high-grade CIN. Non-thermal laser treatment with 100-150 mW/cm2 was well tolerated. Local toxicity was minor as several patients reported burning sensations and vaginal discharge, but no necrosis, sloughing or scarring occurred. After 3 months, a significant reduction in the size of the ectocervical CIN lesions was noted in only 3 patients, who underwent a second PDT cycle. However, no significant improvement in CIN lesions was noted since cold knife conization revealed persistent CIN in all 7 cases. Therefore, PDT after topical application of 5-ALA using an irradiation of 100 J/cm2 produces only minimal side effects. However, it does not appear to be effective in treating CIN.