Recent psychobiologic research has provided new insights into the interplay between constitutional and environmental etiologies in stress-induced childhood illness. Individual differences in both psychobiologic reactivity and physiologic self-regulation may substantially influence a child's internal stress responses. In addition, the physiologic consequences of a given environmental stressor may depend critically on the developmental stage in which the stressor occurs. Behavioral changes associated with early exposures to stressors may be linked to alterations in central nervous system monoamine production and metabolism. Evidence for developmental and psychobiologic changes in response to very early, even prenatal, stressors suggests that environmental and genetic contributions to stress response profiles may ultimately be difficult to disentangle.