A national surveillance program for congenital cytomegalovirus (CMV) disease was initiated in 1990. In 4 years 285 cases were reported without seasonal patterns. Mean birth statistics were as follows: gestational age, 36 weeks; weight, 2,224 g; length, 45 cm; and head circumference, 30 cm. Of the infants 68% had CNS involvement, which was significantly (P < .005) associated with a direct bilirubin level of > or = 3 mg/dL, petechiae, an alanine aminotransferase level of > 100 U/L, a platelet count of < or = 75,000/mm3, hepatomegaly, and splenomegaly (P < .05). Maternal demographics revealed that the mean age was 23 years (range, 13-38 years), 59% were white, 33% were black, 47% had low incomes (receiving Medicaid), and 45% were primiparous. Compared with 1990 birth statistics in the United States, mothers of infants with congenital CMV disease were younger, and a greater percentage of these mothers were black. Two distinct maternal groups were identified on the basis of age, socioeconomic status, and parity. This finding may reflect different modes of transmission and suggest target populations for future CMV vaccine initiatives.