This study investigated dopamine receptor genes ("DRD2" and "DRD4") and maternal sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA reactivity, purported indices of vagal tone and vagal regulation, in a challenge task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear modeling (HLM) revealed that at 3 and 6 months, RSA withdrawal in response to maternal separation was greater (suggesting expected physiological regulation) in infants without the "DRD2" risk allele than those with the risk allele. At 12 months, infants with the risk allele who were also exposed to maternal sensitivity showed levels of RSA withdrawal comparable to infants who were not at genetic risk. Findings demonstrate the importance of developmental analysis of gene-environment interaction.