While cocaine is now used much more frequently than heroin by women of childbearing age, we have found that a significant number of mothers have abused both drugs during their pregnancy. We studied 86 infants who were born to women with a history of cocaine and/or heroin use during pregnancy. The newborns were observed over a 5-day hospital period using a standardized abstinence scoring system and urine drug screening of both mother and infant. Of these, 35 had maternal and/or newborn urine test results that were positive for cocaine only (cocaine group), 14 that were positive for heroin only (heroin group), 17 that were positive for both cocaine and heroin (cocaine/heroin group), and 20 that were negative for both, although the mothers admitted to cocaine use during their pregnancy (cocaine history group). In approximately half of the mother/infant pairs, the results of the urine drug tests were discordant. Microcephaly and growth retardation occurred most frequently in the infants in the cocaine group (17% and 27%, respectively). Microcephaly was also found to be significant in the infants in the cocaine/heroin group. Signs of drug withdrawal occurred in all four drug-exposed groups. Mild withdrawal occurred in 26% of infants in the cocaine group, 21% of the infants in the heroin group, 47% of the infants in the cocaine/heroin group, and in 30% of the infants in the cocaine history group. Withdrawal requiring treatment occurred in 6% of the infants in the cocaine group, 14% of the infants in the heroin group, 35% of infants in the cocaine/heroin group, and 5% of the infants in the cocaine history group. The use of heroin with cocaine has a synergistic effect on the behavior of the newborn.