The results of prior studies suggest that abnormalities of development and function of the fetal adrenal occur in pregnancies complicated by intrauterine fetal growth retardation (IUGR). In the present investigation, we sought to extend such studies by matching IUGR infants with normally grown infants of women in whom pregnancy complications, delivery method, and gestational age were comparable. In 47 vaginally delivered, IUGR infants (38 ± 2 wk, mean ± SD; 2244 ± 589 g body weight), the levels of dehydroepiandrosterone sulfate (DS) in umbilical cord serum (4.48 ± 2.94 μmol/L) were lower (p = 0.035) than those (5.94 ± 3.63 μmol/L) of 47 normal weight infants (38 ± 2 wk; 3107 ± 527 g). Yet, umbilical cord serum levels of Cortisol in IUGR infants (455 ±189 nmol/L) were slightly higher than those of the control infants (408 ± 247 nmol/L). The DS/cortisol molar ratio in IUGR infants (10.5 ± 6.8) was 41% lower (p = 0.0013) than that of the control infants (17.7 ± 13). Also, the estimated DS plasma pool in IUGR infants (521 ± 349 nmol) was strikingly lower (p = 0.0018) than that of the control infants (800 ± 480 nmol); the estimated plasma pools of Cortisol were equivalent (growth-retarded: 53 ± 27 nmol; control: 55 ± 34 nmol). Although we anticipated that total cholesterol and apo B levels in IUGR infants would be increased due to reduced adrenal utilization of LDL for DS production, such was not the case. We conclude that a selective deficiency of DS production occurs in the IUGR fetus. © 1994 International Pediatric Research Foundation, Inc.