The present study examined the relationship between salivary cortisol and maternal responsiveness in mothers of boys with fragile X syndrome (FXS). Maternal responsivity is strongly associated with child outcomes, and children with FXS are at risk for compromised development due to intellectual disability and problem behavior. Increased understanding of the nature and underlying mechanisms of maternal responsivity in FXS is important to optimize outcomes in children with FXS and contribute to improved family cohesion. Data from 36 mother-child dyads indicated a complex age effect with elevated cortisol levels associated with high maternal responsivity scores when children are young and low responsivity scores when children are older. Implications of these findings and directions for future research are discussed.