Background: Impairment in maternal interpersonal function represents a risk factor for poor psychiatric outcomes among children of depressed mothers. However, the mechanisms by which this effect occurs have yet to be fully elucidated. Elevated levels of emotional or physiological reactivity to interpersonal stress may impact depressed mothers' ability to effectively negotiate child-focused conflicts. This effect may become particularly pronounced when depressed mothers are parenting a psychiatrically ill child. Methods: The current feasibility study evaluated mothers' emotional and cardiovascular reactivity in response to an acute, child-focused stress task. Twenty-two depressed mothers of psychiatrically ill children were recruited from a larger clinical trial; half were randomly assigned to receive an adapted form of interpersonal psychotherapy (IPT-MOMS), while the other half received treatment as usual (TAU). For comparison purposes, a matched sample of 22 nondepressed mothers of psychiatrically healthy children was also evaluated. Results: Depressed mothers receiving minimal-treatment TAU displayed the greatest increases in depressed mood, heart rate, and diastolic blood pressure in response to the child-focused stress task, and significantly differed from the relatively low levels of reactivity observed among nondepressed mothers of healthy children. In contrast, depressed mothers receiving IPT-MOMS displayed patterns of reactivity that fell between these extreme groups. Maternal stress reactivity was associated not only with maternal psychiatric symptoms, but also with levels of chronic parental stress and maternal history of childhood emotional abuse. Conclusions: Future, more definitive research is needed to evaluate depressed mothers' interpersonal stress reactivity, its amenability to treatment, and its long-term impact on child psychiatric outcomes. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc.