Folate receptor alpha (FRalpha) expression in epithelial ovarian cancer may be related to folate intake. We examined this association using multivitamin intake, a proxy for folic acid, and assessed whether the relation was modified by alcohol intake, a folate agonist. Cases (n = 148) with suspected epithelial ovarian cancer, of ages > or = 20 years, were seen at Mayo Clinic, Minnesota, between 2000 and 2004; those with tumor specimens (n = 108) were included in analyses. Outpatient controls (n = 148) without cancer and with at least one ovary intact were matched to cases by age (within 5 years) and state of residence. Multivitamin (> or = 4 pills/wk) and weekly alcohol (> or = 5 drinks) intakes were assessed. Tumor specimens were analyzed immunohistochemically for FRalpha. Multivariable rate ratios (RR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. In case-control analysis, the RRs of multivitamin intake with absent/weak/moderate and strong-expressing FRalpha tumors were 0.30 (95% CI, 0.12-0.70) and 0.47 (95% CI, 0.24-0.91), respectively. For alcohol, the associations were 0.84 (95% CI, 0.24-2.86) and 1.65 (95% CI, 0.69-3.93), respectively. In case-case analysis, the RR associated with developing strong-expressing versus other FRalpha tumors was 3.13 (95% CI, 1.14-8.65) for multivitamins and 1.58 (95% CI, 0.45-5.60) for alcohol. The data did not support evidence for an interaction between multivitamin and alcohol intake with risk of developing a strong-expressing FRalpha tumor. The association of multivitamin intake with ovarian cancer may depend on FRalpha expression level.