Accumulating evidence suggests that antenatal depression predicts infants' negative affectivity, albeit with variable effect sizes. With a prospective longitudinal design, we sought to explain that variability by addressing questions about timing of the depression across pregnancy and the early postpartum, the role of high symptom levels relative to diagnosed depression, comorbidity with anxiety, and the potential mediating role of neuroendocrine functioning. Primiparous women (n = 77) with histories of depression prior to pregnancy were assessed for cortisol levels monthly beginning by mid-pregnancy. Depression symptom levels and diagnostic status were similarly assessed monthly in pregnancy and also until infants reached three months of age, when mothers completed the Infant Behavior Questionnaire-Revised to measure infant negative affectivity. Antenatal depression symptoms and infant negative affectivity were positively associated (r = .39). Controlling for depression symptom levels in other trimesters, only second trimester depression symptoms predicted higher infant negative affectivity (beta = .44). With postpartum depression symptom levels in the model, only antenatal depression symptoms predicted infant negative affectivity (beta = .45). In the context of depression, neither antenatal anxiety symptoms nor anxiety disorder diagnosis were associated with infant NA scores. The hypothesized role of elevated maternal cortisol as a mechanism for the association between antenatal depression and infant NA was not supported. Our findings contribute to efforts to more precisely identify infants of perinatally depressed mothers who are at greater risk for elevated negative affectivity, suggesting a window of vulnerability in mid pregnancy and the need for further study of potential mechanisms. (C) 2014 Elsevier Inc. All rights reserved.