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Maternal anxiety and depression were assessed by standardized measures during the third trimester of pregnancy and postpartum. Infant negative behavioral responses to novelty were assessed using a previously validated measure at 4 months of age. Maternal anxiety and depression during the prenatal, but not the postnatal period, were related to infant negative behavioral reactivity to novelty. Maternal stress, anxiety, and depression during infancy have pervasive influences on development including enhanced stress reactivity, poor emotional regulation, and impaired cognitive development. These effects appear to be mediated by disturbances in the quality of mother–child interactions.