Aromatic hydrocarbon hydroxylase (CYP1A1) is involved in the metabolism of many substrates and the subject of cancer studies. This study examined the association between two polymorphic variants of CYP1A1 and ovarian cancer risk. The frequencies of the Msp1 and Ile/Val variants of CYP1A1 were determined in 445 ovarian cancer cases and 472 general population controls in New England. Overall relative risks were calculated as well as those within subgroups of various exposures. There was no increased risk for ovarian cancer associated with possession of either the Msp1 or Ile/Val polymorphism of CYP1A1. Elevated risk for ovarian cancer was found in those who carried an Ile/Val variant and who consumed more than median levels of caffeine (risk ratio = 2.69; 95% confidence interval, 1.18-6.18). No variation by histological type of ovarian cancer was observed. Significant interaction may exist between polymorphic variants of CYP1A1 and caffeine that could explain weak or inconsistent associations between caffeine and ovarian cancer when genotype has not been considered.