Objective-To identify perinatal factors that are predictive of disruption in primary caregiving among infants of substance abusing women.Method-A randomized longitudinal cohort study. One hundred and fifty two mother/infant dyads were assessed for evidence of disruption of primary caregiving or neglect during the first 18 months of life, defined by mother's inability to provide care. Data analyzed included neonatal characteristics, urine toxicology at delivery, maternal history of drug use, maternal depression, social support, and social and health history.Results-Sixty-six infants (43.4%) had disruption in their primary care during the first 18 months of their life. 86 infants (56.6%) remained in the care of their mothers. Women who were younger, were heroin users, had two or more children, had other children in foster care, and reported depressive symptoms were least likely to provide ongoing primary care for their infant.Conclusions-Although all infants born to substance abusing women are at a high risk for disruption in the continuity of their primary caregiving, maternal demographic and psychosocial factors present at delivery can predict which infants are likely to experience an early disruption in their primary caregiving. Identifying these families can enable health care providers to monitor them more closely and, when appropriate, encourage support from the extended family. © 1997