Maternal prenatal stress has been found to be related to over-activity and/or dysregulation of the HPA-system in the offspring. These effects are more readily apparent in response to novel situations. The aim of the present report was to examine whether pregnancy stress predicted HPA-axis reactions of children to the first day of school after the summer break. Children of mothers with more prenatal stress were compared to those of mothers with less stress. Habituation was studied by comparisons between the first school day and a second school day a week later. Finally, cortisol levels at school were compared to those of a weekend day. The participants were 29 mother-child pairs (20 girls and nine boys, mean age 5.31 years, SD = 0.50). The children's cortisol levels were determined in saliva. Multilevel analysis (hierarchical linear modelling) was used to analyze the data. Both prenatal cortisol and pregnancy anxiety were related to the children's cortisol levels as a reaction to the first school day. Children whose mothers had higher levels of morning cortisol during pregnancy, and more fear of bearing a handicapped child showed higher levels of cortisol on school days. In addition, the circadian rhythm of cortisol on school days appeared to have a steeper slope as compared to that of the circadian curve on a weekend day.