In many mammalian species, new mothers show heightened positive responsiveness to infants and their cues when they give birth. As is evident from non‐human and human studies, the amygdala is a brain region implicated in both the maternal and affective neural circuitry, and is involved in processing socioemotionally salient stimuli. In humans, infants are socially salient stimuli to women, and mothers in particular. Neuroimaging studies investigating the maternal response to infant cues have identified infant‐related amygdala function as an important factor in maternal anxiety/depression, in the quality of mothering and in individual differences in the motivation to mother. The present study investigated the effects of maternal status and depression on the subjective affective response and amygdala responsiveness to unfamiliar infants using functional magnetic resonance imaging. Smiling infant pictures were used in a 2 × 2 design comparing four groups of women: mothers and non‐mothers, with and without depression (total of 101 women: postpartum depression [PPD] = 32, non‐PPD = 25, major depression [MDD] = 15, non‐MDD = 29). We undertook an anatomically defined region of interest analysis of the amygdala response for a priori defined group comparisons. We found that mothers rated infants more positively than non‐mothers and non‐mothers rated non‐infant stimuli (scenery) more positively than mothers. In the amygdala, we found that depression elevated response to smiling unfamiliar infants in mothers but had no effect in non‐mothers. Within the depressed groups, mothers (PPD) showed an elevated amygdala response to unfamiliar smiling infants compared to depressed non‐mothers. Hence, our results indicate that women with PPD show an enhanced amygdala response to affectively positive infant pictures but not to affectively positive (but non‐salient) pictures of scenery. Women with depression outside of the postpartum period show no change in amygdala responsiveness to either stimulus categories.