A case-control study was designed to assess the relationship between cervical intraepithelial neoplasia (CIN) and folate in serum, red blood cells, and diet. The association between CIN and dietary vitamin C was also investigated. Cases were selected from women with biopsy-confirmed CIN. Controls were age-, race-, and clinic-matched women with normal cervical (Pap) smears. Study participants completed self-administered food frequency (n = 100 matched pairs) and health (n = 102 matched pairs) questionnaires. Fasting venous blood samples were collected for serum (n = 98 matched pairs) and red cell (n = 68 matched pairs) folate assays. Conditional logistic regression models were used to estimate crude odds ratios and odds ratios adjusted for smoking, income, number of sexual partners, frequency of cervical smear, use of spermicidal contraceptive agents, history of genital warts, and Quetelet index. Dietary intake variables were adjusted for total energy intake prior to logistic regression. A protective effect of red cell folate was evident with adjusted odds ratios (95% confidence intervals) of 0.1 (0.0-0.4), 0.6 (0.2-2.0), and 0.5 (0.2-1.9) for those in quartiles 4 (highest), 3, and 2 compared to quartile 1 (lowest). Supporting evidence for the protective effect of folate was provided by inverse associations between CIN and folate in both serum and diet. An inverse association was also found between CIN and dietary vitamin C with adjusted odds ratios (95% confidence intervals) of 0.2 (0.0-0.7), 0.6 (0.2-1.6), and 0.6 (0.2-1.8) for those in quartiles 4, 3, and 2, respectively, compared to quartile 1. These findings support dietary recommendations, such as those of the American Cancer Society, the National Cancer Institute, and the U.S. Dietary Guidelines, which allow for adequate intake of folate and vitamin C, both of which are found in good quantity in fruits and vegetables. Increased consumption of legumes and whole grains is also in accord with current dietary recommendations, and both of these types of foods are good sources of folates.