The hypothalamus-pituitary-adrenal axis is particularly sensitive to conditions of maltreatment. In particular, neglected children have shown a flatter slope with lower wake-up values relative to nonneglected children. An intervention, the Attachment and Biobehavioral Catch-Up (ABC), was developed to enhance biological and behavioral regulation in young children at risk for neglect. The effectiveness of the intervention was assessed in a randomized clinical trial for children with involvement with Child Protective Services. Following the intervention, children receiving the ABC intervention (n = 49) showed more typical cortisol production, with higher wake-up cortisol values and a steeper diurnal slope, than children receiving the control intervention (n = 51). These results suggest that the ABC intervention is effective in enhancing biological regulation.