This study investigates the role of physiological self-regulation (cardiac vagal tone) in information processing (habituation) in 81 infants. Nucleus ambiguus vagal tone (Vna, a measure of respiratory sinus arrhythmia) was used to index cardiac vagal tone. Physiological self-regulation was operationalized as the change in Vna from a baseline period of measurement to habituation. Decreases in Vna consistently related to habituation efficiency, operationalized as accumulated looking time (ALT), in all infants twice at 2 months and twice at 5 months; however, this relation was accounted for by infants who met an habituation criterion on each task. Among habituators, shorter lookers also had greater Vna suppression during habituation. Within-age and between-age suppression of vagal tone predicted ALT, but ALT did not predict suppression of vagal tone. Physiological self-regulation provided by the vagal system appears to play a role in information processing in infancy as indexed by habituation.