Recent evidence suggests sudden infant death syndrome (SIDS) infants have a diminished capacity to respond to autonomic challenges during a vulnerable developmental period. We speculate that a dysfunction or altered trajectory in the development of the autonomic nervous system may be detected in utero and also may play a role in the pathogenesis of unexplained late stillbirth. Some fetuses, as well as infants, may be more vulnerable than others to autonomic challenges during periods of autonomic instability. Investigation of potential shared underlying mechanisms in both SIDS and unexplained stillbirth will require expanded epidemiological investigation of genetic and environmental correlates along with a systematic study of developmental physiology and neuropathology. As with SIDS, there are likely important interactions between genetic susceptibility and environmental exposures occurring during gestation, which lead to infants who have altered trajectories or deficits in autonomic function and who need to be identified before they enter the periods of greatest risk.