Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is an important feature of major depressive disorder (MDD), but relatively little attention has been given to within-person variability of hormone secretion over time. Because most studies have been conducted in hospital settings, little information is available about naturally occurring patterns of cortisol secretion throughout the day in depressed outpatients. Multiple salivary cortisol samples were obtained over a 6-day period from 47 outpatients with MDD and 39 healthy controls in their everyday environment. We used multilevel regression analysis to estimate the effects of MDD and associated clinical characteristics on cortisol levels and intraindividual variability. Although more severe symptoms were associated with small elevations in cortisol levels, we found no clear evidence for hypercortisolism in the MDD group as a whole. However, cortisol output in MDD outpatients was less stable from sample to sample, as evidenced by a significantly lower autocorrelation than that observed in controls. Secretory patterns were particularly erratic in patients with more severe or recurrent episodes. Findings suggest that erratic cortisol secretion may be a more characteristic feature of HPA axis dysregulation in MDD than hypercortisolism, especially in outpatient populations.