BACKGROUND: Heart rate variability (HRV) reflects autonomic control of the heart. After intrauterine cocaine exposure, asymptomatic newborn infants within 72 hours of life have decreased HRV. It is unknown whether these alterations are transient (acute effect) or persist in older infants and possibly reflect a teratogenic effect of cocaine. METHODS: This study prospectively evaluated HRV in 2- to 6-month-old infants who were exposed to cocaine in-utero (Group 1, n = 71). Their data were compared to normal controls (Group 3, n = 77) and to newborns exposed to drugs other than cocaine (Group 2, n = 89). Based on our previous study, heavy and light cocaine exposure was also defined a priori as the amount of cocaine used during the pregnancy that was more than or less than the 70th percentile, respectively. RESULTS: At the age of 2 to 6 months, infants with in-utero cocaine exposure had higher vagal tone and higher HRV (total power) than normal controls (no exposure to drugs). Most of this increase in vagal tone occurred in the light-cocaine-exposure group. HRV and vagal tone in the heavy-cocaine-exposure group were similar to the noncocaine-exposed group. CONCLUSIONS: At 2 to 6 months of age, asymptomatic infants exposed to cocaine in-utero have recovered from lower HRV seen within 72 hours of age. Infants exposed to light cocaine recovered by a rebound by increasing their vagal tone to above-normal levels. A similar response was blunted in heavily-cocaine-exposed infants. These alterations noted at follow up suggest a possible teratogenic effect of cocaine on the developing autonomic system.