Oral contraceptive (OC) use has been consistently linked to a reduction in ovarian cancer in a dose-dependent fashion. Whether short-term OC use is protective remains controversial. In 1994-1998 in the Delaware Valley of Pennsylvania, the authors examined the association between short-term OC use and ovarian cancer in a population-based case-control study comparing 608 incident epithelial ovarian cancer cases with 926 community controls. Using unconditional logistic regression and adjusting for known confounders, they found a significant reduction in ovarian cancer risk for women who had used OCs for < or =6 months (odds ratio = 0.73, 95% confidence interval: 0.54, 0.99). This protective effect was observed in only that group who had used OCs for < or =6 months and stopped because of side effects (odds ratio = 0.59, 95% confidence interval: 0.40, 0.87 for side effects and odds ratio = 0.91, 95% confidence interval: 0.60, 1.37 for non-side-effects). Women who used OCs for >6 months were at a reduced risk independent of their reason for stopping. Results were similar when stratifying by parity and hormone therapy use. Thus, OC use for as little as 6 months provides significant protection against ovarian cancer risk, protection that appears limited to those women who stop using OCs because of side effects. Mediating factors may reflect endogenous hormone levels, OC metabolism, or OC bioactivity.