Study was made of unconjugated estriol (E) by radioimmunoassay and cortisol (C) by competitive protein-binding assay in the maternal serum (Mat), mixed cord blood (Cord), and amniotic fluid (AF) from 50 pregnancies, 37 or more weeks' gestation (30 normal women, 9 insulin-dependent diabetics; 8 with chronic stress: precclampsia, eclampsia; 3 sets of uncomplicated twins). The normal patients' results were suggestive that Cord E and C were derived from a common precursor or fetal organ activity (r=0.382, P<0.05) and that Mat E, which correlated with Cord E (r=0.432, P<0.05), reflected fetoplacental metabolism. Within 1 hour of delivery, Mat E dropped to<2.0 ng/ml. Insulin-dependent diabetics had values similar to those in the normal population. In chronically stressed patients, the results suggest that stress causes fetal C production to increase relative to E. The Mat E (mean value, 6.18 ±1.23 ng/ml) was significantly less than normal (P<0.01), while the Cord C (mean value, 35.4 ± 4.5 yug/dl) was greater than in the normal baby (P<0.01). Twin pregnancies demonstrated elevated Mat E, but individual Cord E approximated the normal singleton. Paired sample mean ratios of E and C in the various compartments were utilized to differentiate groups of patients. The Mat E/AF E and Mat C/AF E gave meaningful differences that could be clinically useful because of the availability of sampling. The biosynthetic pathways of E and C, the metabolic and compartmental interrelationships, and the control mechanisms are discussed and related to the data.