The use of Papanicolaou smears for cervical cancer screening has led to an increased detection of preinvasive conditions of the cervix, cervical intraepithelial neoplasia (CIN). Epidemiological studies have shown an association between low levels of dietary β-carotene and CIN. In this Phase II study, we have explored the effect of p.o. β-carotene administration on CIN I and II. Patients with documented CIN I or II were treated with 30 mg daily of β-carotene for 6 months. Response rates were determined at 0, 3, 6, and 12 months with cytology, colposcopy, and/or biopsies. Levels of β- carotene and vitamin E were determined at the same time intervals in vaginal mucosa cells and serum. Response rates were 18 of 30 (60%), 21 of 30 (70%), and 10 of 30 (33%) at 3, 6, and 12 months, respectively. Significant changes occurred in the serum β-carotene levels over time. Median levels over 2200 mg/ml were found at 3 and 6 months versus a baseline median level of 111 (P < 0.0001). Significant increases were also noted in the β-carotene levels of the vaginal mucosa compared to baseline (P = 0.01) and a significant correlation was noted between serum and vaginal β-carotene levels as well (P < 0.0001). This study indicates that a large percentage of patients with CIN I and II will respond clinically to p.o. β-carotene supplementation. There is a positive relationship between serum and tissue levels of β-carotene which suggests that serum levels can be used for monitoring purposes. Because of these encouraging results, prospective randomized studies are ongoing comparing the efficacy of β-carotene against an untreated control arm.