The purpose of this study was to assess the relationship between maternal drug use during pregnancy, which was identified by positive toxicology screening tests, and subsequent neonatal assisted ventilation. The study population consisted of 38,762 women and their babies who were born alive in 1995 or 1996 at 7 Northern California Kaiser Permanente hospitals with neonatal intensive care nurseries (NICU's). Data available on each mother-infant pair included demographics, toxicology screen results (including specific drugs for which each screen was positive), NICU admission status, and neonatal assisted ventilation use. Overall, 4.2% of mothers (n=1642) had at least one positive toxicology test during their pregnancy. Of the 11 drugs tested for, the following 5 were considered most harmful to the fetus and were used either singly or in combinations by 965 of the women who ever tested positive: alcohol (n=197 women ever tested positive, 0.5% of the total), amphetamines (n=161, 0.4%), methamphetamines (n=183, 0.5%), cocaine (n=91, 0.2%), and tetrahydrocannabinol (THC) (n=666, 1.7%). Women were counted once for each drug for which they ever tested positive. In this 2-year cohort, 2.7%(n=1034) of all babies required assisted ventilation. Significantly more babies of mothers ever found positive for any of the 5 most harmful drugs required assisted ventilation (5.4%) than those who did not test positive(2.6%; Chi square test, p=0.001). This finding was driven by the results for intermediate low birthweight babies between 1500 and 2499 grams, in which 26.3% of babies whose mothers tested positive for one of the 5 most harmful drugs required assisted ventilation compared to 13.2% of the babies whose mothers did not test positive for any of those drugs (p=0.001). These results suggest that babies of mothers who tested positive for alcohol, amphetamines, methamphetamines, cocaine or THC during pregnancy are significantly more likely to require assisted ventilation than babies of mothers who do not test positive for those drugs, particularly in the intermediate low birthweight category. The morbidity experienced by these babies and the costs of associated neonatal services are enormous. Identifying drug-using women early in pregnancy and providing rehabilitation programs might lower morbidity and neonatal services costs considerably.