Background: A study was designed to examine the association between prenatal tobacco exposure (PTE) and infant cortisol reactivity of children 9 months of age. Data was obtained from 217 participants and the results were fruitful. They indicated that there is a significant association between PTE and infant cortisol that was moderated by infant sex and maternal intrusiveness. Among the male sex, it was found that PTE boys had lower cortisol levels than the control boys. On the other hand, there was no association between PTE and cortisol in girls. The study also discovered that infants of intrusive mothers had a significant association between PTE and cortisol while infants with non-intrusive mothers did not. Drawn from these findings is the conclusion that PTE was associated with cortisol hypo-reactivity such that boys and non-exposed infants experiencing high maternal intrusiveness were at greater risk.