We conducted a case-control study to investigate the effect of prepregnancy diet, particularly dietary fats, on the risk of severe hyperemesis gravidarum. Cases were 44 women previously hospitalized at Brigham and Women's Hospital, Boston, MA, for severe hyperemesis gravidarum who delivered a singleton liveborn between January 1, 1993, and December 31, 1995. Controls were 87 women who delivered a singleton liveborn at Brigham and Women's Hospital during the same period and who experienced less than 20 hours of nausea and fewer than three episodes of vomiting over the duration of their pregnancies. Odds ratios were derived from unconditional logistic regression models using data collected via self-administered food frequency questionnaires. Our results indicate that prepregnancy, high daily intake of total fat increases the risk of severe hyperemesis gravidarum (odds ratio = 2.9 for each 25 gm per day increase; 95% confidence interval = 1.4-6.0). This association is driven primarily by saturated fat intake [odds ratio = 5.4 for each 15 gm per day increase (equivalent to one quarter-pound cheeseburger); 95% confidence interval = 2.0-14.8]. We observed no independent effect of total energy intake.