OBJECTIVE: Our purpose was to characterize the fetal adrenal response to acute intrapartum stress in otherwise uncomplicated pregnancies. STUDY DESIGN: Term infants (n = 61) diagnosed as having fetal distress during labor, as indicated by heart rate abnormalities, and delivered of women having normal pregnancies were pair-matched with 61 infants showing no signs of fetal distress or acidemia (controls) on the basis of gestational age and delivery method. Umbilical cord serum dehydroepiandrosterone sulfate and cortisol were measured, and the data were analyzed by two-tailed t test, Fisher's exact test, analysis of variance, and Tukey's multiple range test. RESULTS: Distressed infants had lower serum levels of dehydroepiandrosterone sulfate (3992 ± 246 nmol/L, mean ± SE) than control infants (4853 ± 283 nmol/L); distressed infants also had higher levels of cortisol (412 ± 17 nmol/L) than did control infants (299 ± 16 nmol/L). The dehydroepiandrosterone sulfate/cortisol ratios in control infants (17.7 ± 1.2) were almost twice those of distressed infants (10.8 ± 0.9). These same relationships also were noted when the infant pairs were segregated according to whether delivered vaginally (21 pairs) or by cesarean section (40 pairs). The abnormalities in steroid levels in the distressed infants were independent of the presence or absence of acidemia. CONCLUSION: Intrapartum stress acutely alters fetal adrenal steroidogenesis, leading to increased production of cortisol and decreased secretion of dehydroepiandrosterone sulfate. © 1993.