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While biological and behavioral stress response systems are intact in early gestation, preterm infants' behaviors are often more subtle and difficult to interpret compared with full-term infants. They are also more vulnerable for regulatory issues (ie, colic) that are known to impact caregiver–infant interactions. Biobehavioral measures such as behavioral responsivity and heart rate variability (HRV), particularly cardiac vagal tone, may help elucidate preterm infants' stress/regulatory systems.To test the hypotheses that preterm infants' consoling behaviors and high-frequency (HF) HRV in the first week of life are significantly associated and they are inverse correlates of future colic risk.Thirty preterm (mean ± SE = 32.7 ± 0.3 weeks postmenstrual age [PMA]) infants underwent direct NIDCAP (Newborn Individualized Development and Assessment Program) observation during routine care and had HRV measurements during their first week postbirth. Sixty-three percent of mothers completed the Infant Colic Scale at 6 to 8 weeks adjusted postnatal age. Nonparametric tests were used to determine associations among behaviors, HRV, and maternal perceptions of infant colic.Self-consoling behaviors were positively associated with HF-HRV (vagal tone). In addition, stress behaviors were positively associated with low-frequency/high-frequency HRV (sympathetic dominance). Infants who displayed more stress behaviors also demonstrated more self-consoling behaviors. No significant associations were found with colic.HF-HRV provides information on the infant's capacity to modulate stress and is a useful, noninvasive measure when behaviors are more difficult to discern.Further study in a larger sample is needed to determine whether behavioral stress measures and HF-HRV may be useful to determine colic risk.