Perineal talc use has been suggested as a possible risk factor for ovarian cancer based on its structural similarity to asbestos, a known human carcinogen. A population-based epidemiologic case-control study of epithelial ovarian cancer (EOC) was conducted in 22 counties of Central California that comprise the reporting area for 2 regional cancer registries. Telephone interviews were conducted with 256 cases diagnosed in the years 2000–2001 and 1,122 controls frequency-matched on age and ethnicity. The interview obtained information on demographic factors, menstrual and reproductive experience, exogenous hormone use, surgical history and family history of cancer. Questions on perineal talc use included frequency of use, duration of use and specific years when talc was used. Multivariate-adjusted odds ratio (OR) and 95% confidence intervals (CI) were derived from unconditional logistic regression. The OR for ever use of talc was 1.37 (CI = 1.02–1.85) compared to never users. However, no dose response association was found. Tubal ligation (TL) modified the effect of talc on EOC such that women with TL had an OR of 0.88 (CI = 0.46–1.68) associated with perineal talc use, whereas women with no TL had an OR of 1.54 (CI = 1.10–2.16). Talc use and EOC risk was highest in women with serous invasive tumors (OR = 1.77; CI = 1.12–2.81). This study provides some support for the hypothesis that perineal talc use is associated with an increased risk of EOC. © 2004 Wiley-Liss, Inc.