Term neonates (n = 74) exposed antenatally to cocaine, methamphetamine, or cocaine and a narcotic but without any other known perinatal complications were prospectively examined with cranial ultrasonography to detect the presence of central nervous system injury. These studies were compared with those of a drug-free but clinically ill group of infants (n = 87) at risk for hypoxicischemic encephalopathy, and with those of infants who were well. Cranial abnormalities were detected by ultrasonography in 35.1% of the drug-exposed infants, similar to the incidence in the infants at risk for hypoxic-ischemic injury (p = 0.7) but significantly greater than the 5.3% incidence of abnormalities in normal infants (p less than 0.001). The lesions in the drug-exposed infants were intraventricular hemorrhage, echodensities known to be associated with necrosis, and cavitary lesions; they were focused in the basal ganglion, frontal lobes, and posterior fossa. The presence of ultrasonographic abnormalities was not predicted by standard neonatal clinical assessment or by other perinatal risk factors present in the drug-using population. The types of cerebral injury are consistent with those seen in adult cocaine and methamphetamine abusers and are probably related to the vasoconstrictive properties of these drugs. Antenatal exposure to stimulant drugs is associated with significant risk for cerebral injury, even among seemingly normal term neonates.