Background: The goal of this study was to evaluate the interactions of mothers with normative or high levels of depressive symptomatology on the Center for Epidemiologic Studies-Depression Scale (CES-D) and their 3-month-old infants. Although successful mutual regulation of affect is critical to children's socio-emotional development, little is known about the factors that influence dyadic processes such as synchrony, matching, mismatching, and bi-directionality during early infancy. Therefore, this study evaluated the effects of maternal depressive symptom status, infant gender, and interactional context on mother-infant affective expressiveness and the dyadic features of their interactions. Methods: Participants were 133 mothers and their healthy full-term infants. Mothers were classified into three groups on the basis of their total score on the CES-D at 2 months of infant age: a high symptom group (CES-D score greater than or equal to 16), a mid symptom control group (CES-D score = 2-12), and a low symptom group (CES-D score = 0-1). Mothers and infants were then videotaped in the Face-to-Face Still-Face paradigm at 3 months of infant age. The mothers' and infants' affect during the interactions prior to (first play) and following the still-face (reunion play) were coded microanalytically using Izard's AFFEX system. Results: Results indicated that male as compared to female infants were more vulnerable to high levels of maternal depressive symptoms and that high symptom mothers and their sons had more difficult interactions in the challenging reunion episode. Conclusions: The findings suggest that a cycle of mutual regulatory problems may become established between high symptom mothers and their sons, particularly in challenging social contexts. The long-term consequences of this early social interactive vulnerability in terms of later development need to be further investigated.