Respiratory sinus arrhythmia (RSA) and heart period were evaluated in 5-month-old infants (N = 40) during interaction challenges requiring affective adjustment. The paradigm consisted of four 2-min experimental conditions designed to elicit behavioral and autonomic responses to object-mediated (Picture Attention and Toy Attention) and person-mediated (Still Face and Social Interaction) engagement. The data demonstrated that autonomic state systematically changed during engagement and disengagement with the environment. During the object-mediated challenge, increases in RSA were uniquely related to positive engagement. During the person-mediated challenge, there was a more complex integration of autonomic and behavioral responses characterized by concordant increases and decreases in RSA, heart period, positive engagement, negative affect, and motor activity. When participants were partitioned into two groups, based on their RSA response pattern during the person-mediated challenge, only participants who exhibited a pattern of RSA decrease from Toy Attention to Still Face followed by a rapid recovery during Social Interaction demonstrated regulation of behavioral activity, including concordant recovery from stress. These findings provide additional empirical support for the role of vagal regulation of the heart in the modulation of affective adjustment and engagement behavior.