Background and Methods. There has been a recent, dramatic increase in the incidence of congenital syphilis, particularly in urban areas. We describe seven infants seen during one year who were first given a diagnosis of congenital syphilis at 3 to 14 weeks of age, when symptoms developed. We reviewed these infants' charts in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants. Result. At delivery, four of the infants and their mothers had negative qualitative rapid-plasma-reagin tests for syphilis. The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of their infants were seronegative at birth, and one was not tested. When the infants became symptomatic between 3 and 14 weeks of age and were admitted to the hospital, all seven infants and the five mothers available for testing were found to be seropositive for syphilis. Four infants presented with a characteristic diffuse rash; the other three presented with fever and were found on admission to have aseptic meningitis. All these infants had multisystem disease, as evidenced by hepatomegaly, increased aminotransferase and alkaline phosphatase levels, anemia, and monocytosis. In all the infants syphilis responded to parenteral penicillin. Conclusions. Congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery. Even when these tests are performed, some infants are not identified as having syphilis, probably because the infection is very recent and there has been insufficient time for an antibody response to develop. Some infants with congenital syphilis of later onset do not present with a typical rash; therefore, at least in areas where the disease is prevalent, serologic tests for syphilis should be included in the evaluation of all febrile infants, even those with negative results on serologic testing at birth. (N Engl J Med 1990; 323:1299–302.).