The purpose of the study was to examine demographic, immune, endocrine, stress and health characteristics of depressed mothers, measured between 4 and 6 weeks postpartum, and compare them to non-depressed mothers. The top decile (N=25) of Profile of Mood States depression scores was used to categorize mothers as depressed and these data were then compared to means of the remaining mothers (N=175) in a study of stress and immunity during the postpartum. Depressed mothers were younger, had smaller birth weight infants, and their babies experienced more illness symptoms at 4-6 weeks postpartum. Depressed mothers were less likely to be breastfeeding and had lower serum prolactin levels. Depressed mothers were more likely to smoke, to have daytime sleepiness, and more symptoms of infection than non-depressed mothers. Depressed mothers also had higher perceived stress, postpartum stress, and negative life event reports. There was evidence suggesting that depressed mothers had a downregulated hypothalamic-pituitary-adrenocortical (HPA) axis, in that salivary cortisol was lower in depressed mothers. Depressed mothers also had lower serum levels of Interferon-gamma (IFN-gamma) and a lower IFN-gamma/Interleukin-10 (IL-10) ratio in both sera and in whole blood stimulated cultures, suggesting a depressed Th1/Th2 ratio in depressed mothers. The data supports the possibility that postpartum depression may be associated with a dysregulated HPA axis and possible depressed cellular immunity.