The incidence of congenital syphilis has recently reached epidemic proportions. With the resurgence of this important clinical entity, currently recommended screening procedures may be inadequate. We describe three cases that highlight the limitations of these screening procedures. All these infants had associated maternal risk factors for congenital syphilis, such as poor prenatal care and illicit drug use. All the infants and mothers were seronegative for syphilis at the time of birth but the infants became seropositive at 2 months of age. These cases support the need to reexamine current screening policies. In addition to prenatal and at-delivery screenings for congenital syphilis, it may be appropriate to screen infants born to high-risk mothers at 4 to 8 weeks of age.