The current management of vaginal intraepithelial neoplasia (VAIN) often involves the use of laser vaporization. A study was performed to measure the epithelial thickness in both premenopausal and postmenopausal women with various grades of VAIN to determine the optimum depth of tissue destruction if laser vaporization is used for therapy. Hematoxylin and eosin-stained tissue sections were examined with light microscopy and measurements made with a calibrated micrometer. Sixty-three biopsies from 56 patients were studied. Patients' ages ranged from 22 to 84 years, with a mean of 56. Thirty-six had a prior history of cervical neoplasia. Thirty-nine patients (70%) had VAIN III, 10 had VAIN II, and the remaining 7 patients had VAIN I lesions. The involved epithelium varied from 0.10 to 1.4 mm in thickness, with a mean of 0.46. Noninvolved vaginal epithelium varied in thickness from 0.10 to 0.70 mm, with a mean of 0.28. Koilocytosis was noted in only 9 of the 63 biopsy specimens. In comparing the thickness of involved epithelium in a given patient to that of an adjacent area of normal-appearing epithelium, the epithelium containing VAIN tended to be thicker. The recommended depth of epithelial destruction with laser vaporization in the literature varies widely and appears to have largely an empiric basis. Our study attempted to provide a scientific basis for laser destruction of these lesions. The results obtained indicate that epithelial destruction to a depth of 1.5 mm, including the zone of thermal necrosis, should be sufficient to destroy epithelium containing VAIN without damage to surrounding structures.