This prospective study examined whether neonates of pregnant women who used cocaine during pregnancy are at a risk for the development of transient myocardial ischemia and altered autonomic function, as in adults. We studied 21 of 35 infants with a history of prenatal exposure to cocaine. The ST segment changes and heart rate variability were evaluated from three-channel Holter monitors within 48 hours of birth. The data were compared with those on 20 control infants with similar birth weight, gestational age, and postnatal age. Six infants (29%) who were exposed to cocaine in utero had transient ST segment elevation, versus only one infant (5%) from the control group (odds ratio = 7.6; 95% confidence interval, 1.14, 50.64). Heart rates, results of total power and low-frequency power spectral analyses for heart rate variability, and arrhythmias were not significantly different in the two groups. However, a lower ratio of low-to high-frequency power reflected increased vagal activity in cocaine-exposed infants. We conclude that cocaine use in pregnant mothers is associated with transient ST segment abnormalities in their infants. These abnormalities are consistent with transient myocardial ischemia.