We conducted a case-control study to determine whether job strain (or stress) during pregnancy resulted in an increased risk of preeclampsia. We compared 110 nulliparous Caucasian and African-American women who had preeclampsia with 115 healthy nulliparous controls. All subjects gave birth between 1984 and 1987 in Chapel Hill, NC. Occupation was ascertained during a telephone interview. We assigned each job title a strain (or stress) score in accordance with the occupational database developed by Karasek. Overall, 54 (49%) of the control women worked during pregnancy, 14 in high-stress jobs. Logistic regression analysis indicated a 3.1-fold [95% confidence interval (CI) = 1.2-7.8] increased risk of preeclampsia for women employed in high-stress jobs (high psychological demand, low decision latitude) and an odds ratio of 2.0 (95% CI = 1.0-4.3) for low-stress jobs compared with nonworking women, while simultaneously adjusting for age, race, family history of preeclampsia, history of hypertension in the subject's mother, gravidity, smoking during pregnancy, timing of the first prenatal visit, and type of birth control used by the couple before the pregnancy. Furthermore, working women had 2.3 times the risk of developing preeclampsia (95% CI = 1.2-4.6) compared with nonworking women. Work-related psychosocial strain increased the risk of preeclampsia in our study.