Complex methodologic challenges face researchers studying the effects of prenatal cocaine exposure on infant outcome. These include unavoidable imprecision in ascertaining the gestational timing and dose of cocaine to which the fetus was exposed and difficulties in identifying and quantifying the confounding, mediating, and moderating variables. Review of research on neonatal behavioral and cranial ultrasound findings following in utero cocaine exposure is used to illustrate these issues. We conclude that there are measurable but not dramatic dose-related effects of prenatal cocaine exposure on infant central nervous system structure and function. The effects of dose of prenatal cocaine exposure on later child development remain to be determined. Such research would be facilitated by a scientific consensus delineating relative doses of prenatal cocaine exposure.