A series of 132 cases of vaginal intraepithelial neoplasia (VAIN) is presented, including nine (6.8%) where early invasive carcinoma of the vagina was found in the course of initial management of the VAIN. The majority of patients (75%) had high-grade VAIN (two or three). Seventy-two (55%) had undergone a prior hysterectomy; 22 for preinvasive disease (CIN), 33 for invasive gynecological cancer, 13 for benign reasons, and in 4 the reason for the hysterectomy and/or the Pap smear history was not known. Twenty-one (16%) had received prior pelvic radiotherapy. VAIN was noted to involve either the vaginal vault (in the post-hysterectomy group) or the upper vagina (in the no hysterectomy group) in more than 80% cases. A variety of treatment modalities was used with varying degrees of success. For high-grade VAIN excisional treatments had an overall (first-line plus subsequent) cure rate of 69% (53/77). The state of the surgical margins did not correlate with the risk of residual disease. CO2 laser ablation was curative in 69% (18/26) of cases and was significantly better than electrocoagulation diathermy which was curative in only 25% (3/12) of cases (P = 0.013). Five-fluorouracil cream was curative in 46% (5/11) of cases, including four patients who had received prior radiotherapy. Radiotherapy was effective in eradicating VAIN in the two cases where it was used as the primary treatment modality. Progression of high-grade VAIN to invasive cancer occurred in eight (8%) cases; after no treatment in two cases, after treatment failure in five cases, and as a late recurrence in one case. For low-grade VAIN an observational approach after biopsy was initially adopted in eight patients and regression occurred in seven (88%) of these patients. Other miscellaneous treatments were also effective in low-grade VAIN. These data provide evidence that high-grade VAIN is a precursor to invasive cancer of the vagina and every attempt should be made to eradicate it. Based on our experience and a review of the literature we have proposed a plan for optimal management of this condition.