Little is known about factors that favor the development of cervical atypical squamous cells of undetermined significance (ASCUS), nor how these factors might affect the pathogenesis of cervical neoplasia. The primary focus of this case-control study among the multiethnic population of Hawaii was to identify biomarkers of diet in the recent past that may influence the risk of ASCUS, after carefully accounting for the presence of HPV DNA. Cases included 185 women with ASCUS and 191 cytologically-normal controls diagnosed between 1992 and 1996 from three clinics in Honolulu, Hawaii. In-person interviews were conducted in the subjects' homes, a fasting blood sample was drawn to measure plasma levels of various micronutrients, and the presence and type of HPV was determined in exfoliated cell samples using Polymerase Chain Reaction (PCR) dot blot hybridization. As results, we found an inverse dose-response gradient with increasing plasma concentrations of &mgr;-cryptoxanthin and &mgr;-tocopherol for the development of ASCUS. The odds ratio for ASCUS among women in the highest quartile compared with women in the lowest quartile of total cryptoxanthin was 0.5 (95% confidence interval (CI): 0.3-1.0), &mgr;-cryptoxanthin was 0.4 (0.2-0.8), total tocopherol was 0.5 (0.2-1.0), &mgr;-tocopherol was 0.5 (0.2-1.0), and &mgr;-tocopherol was 0.4 (0.2-0.8). Little association of plasma levels of lutein/zeaxanthin, lycopene, &mgr;- or &mgr;-carotene, retinol, vitamin C, or cholesterol, with disease risk was evident. Our findings suggest that women with high circulating concentrations of cryptoxanthin and tocopherol may be at a reduced risk of ASCUS.