This manuscript reports on the effects of stressors repeated at a 24-hr interval on three samples of human newborns. In Study 1, newborns meeting criteria for obstetric and perinatal optimality experienced either 2 mock Discharge Exams, viewed as a type of handling stressor, or 2 Heelstick Blood Draws, viewed as a type of nocioceptive stressor. As in a previous study, newborns meeting optimality criteria showed habituation of the adrenocortical response to the repeated Discharge Exam. The adrenocortical response to the repeated Heelstick tended to increase or sensitize. In Studies 2 and 3, samples of newborns with more nonoptimal obstetric complication scale scores were examined. These newborns failed to show habituation of the adrenocortical response to the Discharge Exam, but responded like "Optimal" newborns to the repeated Heelstick. The applicability to these data of the Groves and Thompson (1970) Dual-Process Model of Habituation is discussed. The results also provided evidence of stability in behavioral distress independent of stability in adrenocortical activity. The implications of these data for studies using cortisol as an index of the physiological basis of early temperament are considered.