Maternal depression is associated with problematic parenting and the development of emotional and behavior problems in children and adolescents. While emotional regulatory abilities are likely to influence emotional exchanges between parents and teens, surprisingly little is known about the role of emotion regulation during parent-child interactions, particularly in high-risk families. Respiratory sinus arrhythmia (RSA) has been widely linked to emotion regulatory abilities in recent research, and the current study investigated RSA and maternal depression in relation to dyadic flexibility, as well as mutuality of negative and positive affect displayed during three discussion tasks between 59 mother-adolescent pairs (age 11-17 years). Dyadic flexibility was predicted by the interaction of maternal depression, maternal RSA, and teen RSA, with higher maternal RSA predicting greater dyadic flexibility, particularly in highest risk dyads (i.e., elevated maternal depression and lower teen RSA). Teen RSA interacted with maternal depression to predict mutual negative affect, serving as a protective factor. Finally, maternal and teen RSA interacted to predict mutual positive affect, with maternal RSA buffering against low teen RSA to predict higher mutual positive affect. Results support the role of RSA in affectively laden interactions between parents and adolescents, particularly in the face of maternal depression.