The association between behavioral distress and adrenocortical activity was examined in two experiments with human newborns. In Experiment 1, behavioral and adrenocortical responses to 4 events (circumcision, blood sampling, weighing and measuring, and discharge examination) were compared using a between‐subject design. All 4 events elicited fussing and crying and elevations in plasma cortisol; however, differences in behavioral distress among conditions did not reliably predict differences in plasma cortisol. In Experiment 2, nonnutritive sucking was used to effectively reduce behavioral distress, but was not associated with a reduction in the adrenocortical response to stimulation. Finally, using data from both experiments, correlations were computed between behavioral distress and cortisol. Both positive and negative associations were found as a function of the type of stressor and the biomedical status of the newborn.