Maternal hyperthermia during embryogenesis has been postulated to cause a variety of major congenital anomalies in exposed offspring. Although the literature regarding human exposures is not conclusive, studies using animal models support the contention that major structural anomalies may be produced. In the present study, pregnancy outcome of a cohort of women who reported having a temperature of 101 degrees F or higher for 24 hours or more during the first trimester was compared to a control group of women (matched on last menstrual period, parity, and age) who denied having a fever. A statistically significant increased frequency of a specific type of congenital anomaly, abdominal wall defects, was found in offspring whose mothers had sustained high temperatures during embryogenesis. Although an increased risk of this type of congenital anomaly is not consistent with previous epidemiologic studies, similar defects of this organ system have been reported in offspring of pregnant nonhuman primates (monkeys) and rodents (guinea pigs) who experienced hyperthermia during pregnancy.