In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-III-R categories 3 to 5), in combination with an inadequate social network. They were compared with 50 non-stressed women with an intact social network. Stress and smoking significantly affected birthweight and head circumference. When birthweight was corrected, stress remained a significant determinant of small head circumference, indicating a specific effect on brain development. Stress also led to a suboptimal Prechtl neonatal neurological score. These findings suggest the existence of a fetal stress syndrome with adverse effects on fetal development, including deficient brain development.