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This study examined the association of 6-week maternal self-report depressive symptoms measured by the Center for Epidemiological Studies-Depression Scale (CES-D) with 4-month infant vocal affect qualities. This was part a larger study which examined many additional domains of both infant and maternal behavior. Infant vocal affect qualities were examined in 122 4-month old infants during face-to-face play in relation to 6-week maternal depressive symptoms. Mothers were categorized depressed (26.2%) based on a 16+ cutoff on the CES-D. Videotaped interactions were coded on a 1-s time basis for infant vocal affect qualities (high positive, neutral/positive, fuss/whimper, cry, angry protest and silent.) Infants of depressed mothers were more vocally activated in both positive and negative qualities. In addition, infants of depressed mothers were more vocally variable, specifically in and out of fuss/whimper, as well as more likely to change, rather than maintain vocal states.