During the last decade, several publications have appeared associating the maternal use of cocaine and subsequent development of necrotizing enterocolitis (NEC). In 1994, the effects of cocaine in pregnant rats had been reported by this group: a significant decrease in the number of live births, mean birth weight and mean placental weight. In addition, histopathologic examinations revealed severe inflammation and degenerative vascular changes in the uterus and placenta. Severe histopathologic changes resembling NEC such as focal necrosis, necrobiosis, and hemorrhagic inflammatory changes in the gastrointestinal tract of the embryos were also reported. The aim of the second part of this study was to assess the hemodynamic effects of cocaine HCl in pregnant rats and the results of perfusion studies in the uterus, placenta, and fetuses to determine a relation between the dose of drug, hemodynamic changes, and degree of histopathologic findings. Forty-seven Wistar albino rats and 91 rat fetuses were studied: group A (pregnant rats), 16 rats and 91 rat fetuses, group B (nonpregnant rats), 31 rats. Each group was divided into subgroups of cocaine-abused and non-cocaine-abused rats. In each group 2-3 mCi technetium Tc-99m methoxyisobutyl-isonitryl (Sesta MIBI) was injected into the tail vein. Radioactivity counts per g tissue (cps/g) in the uterus, placenta, and fetus were assessed by gamma counter. Cocaine 75 mg/kg per day severely decreased the perfusion of the uterus, placenta, and fetuses. These impairments were statistically significant. Tn lower doses (30-50 mg/kg per day) no statistically significant changes were observed in the perfusion of the uterus and placenta, but a significant decrease in fetal perfusion was seen. In group B, no significant changes in the perfusion of the uterus due to cocaine were seen. Thus, maternal cocaine abuse results in a reduction in perfusion of the uterus, placenta, and fetus. There was a dose-dependent correlation between the perfusion changes and the development of NEC-like histopathologic changes: the higher the cocaine dose received by the mother, the higher the level of placental and fetal injury. We suggest that perinatal cocaine exposure should be considered a high risk for development of NEC in rat fetuses and embryos. For this reason, infants with a history of possible maternal cocaine abuse or positive urinary cocaine metabolites have to be followed very carefully for NEC.