 1998 John Wiley & Sons, Inc. CCC 0012-1630/98/040327-11 Mary C. Larson Barbara Prudhomme White Amy Cochran Bonny Donzella Megan Gunnar Institute of Child Development University of Minnesota Minneapolis, MN 55455–0345 Dampening of the Cortisol Response to Handling at 3 Months in Human Infants and Its Relation to Sleep, Circadian Cortisol Activity, and Behavioral Distress Received 3 September 1997; accepted 31 March 1998 ABSTRACT: The decrease in responsiveness of the hypothalamic–pituitary–adrenocortical (HPA) system is marked over the first months of life. Seventy-eight healthy infants (44 girls), 7 to 15 weeks old, were given a laboratory mock physical examination. Salivary cortisol sam- ples were collected pre- and postexamination and at home. Behavioral state during the ex- amination and home sleep/wake activity were measured. Subjects younger than 11 weeks showed an increase in pre- to postexamination cortisol, while older subjects did not. Further, there was no decrease in behavioral distress to the examination with age. Infants who showed an early- morning peak (EMP) in home cortisol levels were significantly older and were likely to be those who slept through the night. However, the presence of an EMP was not associated with a lack of cortisol response to the examination. The decrease in cortisol responsiveness witnessed around the age of 3 months is presumably due to other processes associated with age, and not with the expression of the day–night rhythm in basal cortisol.  1998 John Wiley & Sons, Inc. Dev Psychobiol 33: 327– 337, 1998 Keywords: human; stress; cortisol; crying; circadian rhythm; sleep; HPA axis The hypothalamic – pituitary – adrenocortical (HPA) system is one of the two major peripheral arms of the mammalian stress system (Stratakis & Chrousos, 1995). The primary end product of the HPA system in humans is cortisol, a steroid hormone. Elevations in Correspondence to: M. R. Gunnar Contract grant sponsor: NIMH Contract grant number: MHY 00946 Contract grant sponsor: NICHD Contract grant number: HD 16494 cortisol and in corticotropin releasing hormone (CRH) play key roles in mobilizing energy stores, modulating immune system activity, and orchestrating behavioral and physiological (e.g., sympathetic nervous system) responses to potentially threatening events (Munck, Guyre, & Holbrook, 1984; Schulkin, McEwen, & Gold, 1994). A functioning HPA system is essential to survival in even moderately challenging environ- ments. However, activation of this system also carries potential biological and behavioral costs (Ca-