Introduction: This article examines regulatory behaviors and physiological stress reactivity among 6-15 month-old infants with moderate to heavy prenatal alcohol exposure (PAE), a group at very high risk for fetal alcohol spectrum disorders and self-regulation impairments, compared to low risk infants with no/low exposure. Participants: Eighteen infants and their biological mothers; nine infants [M = 10.7 (3.1) months] had moderate to heavy PAE and nine [M = 10.7 (2.9) months] had no/low exposure. Methods: Infant biobehavioral responses to the Still Face Paradigm (SFP), a standardized infant social stressor, were examined. Infant behaviors were compared across: 1) play; 2) still-face (stressor); and 3) reunion conditions, using the Infant and Caregiver Engagement Phases coding system. Salivary cortisol samples were taken at baseline, 15 and 30 minutes post SFP. Mothers completed the Infant-Toddler Symptom Questionnaire (ITSC) and Infant Behavior Questionnaire-Revised (IBQ-R). Results: Infants with PAE had significantly higher baseline salivary cortisol levels [0.26 mg/dl (0.12 SD)] than controls [0.11 mg/dl (0.03 SD; p = 0.05]. Behaviorally, infants with PAE demonstrated significantly fewer social monitoring behaviors compared to controls. There were no significant group differences on caregiver-reported regulatory behaviors (ITSC) or temperament characteristics (IBQ-R). Conclusion: Biobehavioral findings revealed greater stress vulnerability and heightened risk for regulatory problems among infants with high-risk levels of PAE. Results need confirmation with a larger sample. These exploratory findings inform future studies designed to investigate early developmental problems among children with PAE and FASD, and support an overarching goal to improve early identification and early intervention strategies for a group of high-risk infants.