The present study examined the combined influences of maternal depression and attachment security on infants' brain activity and autonomic activity. Brain electrical activity, heart rate, and vagal tone were recorded from 159 13-15 month old infants of depressed, subthreshold depressed, and nondepressed mothers during a baseline and two social interaction conditions. Attachment behavior was observed during the traditional Strange Situation. It was found that infants of depressed mothers exhibited reduced left relative to right frontal brain activity during all conditions. Moreover, regardless of mother's depression status, insecurely attached infants exhibited relative reduced left frontal brain activity. Infants of depressed mothers were also found to exhibit higher heart rates across all conditions. These results indicate that both maternal depression and attachment security are associated with alterations in infants' psychophysiological responses. © 2001 Elsevier Science Inc.