To determine factors that influence the occurrence of congenital cytomegalovirus (CMV) infection, the authors surveyed prospectively 8,254 infants born in eastern Iowa between October 1989 and June 1994. The authors conducted a case-control study to identify maternal risk factors, matching each CMV-infected infant with three uninfected infants according to hospital and date of birth. CMV strains were compared by using the polymerase chain reaction (PCR) to identify common sources of infection. Of the 7,229 infants cultured successfully for CMV, 35 (0.48%) were congenitally infected. Mothers of CMV-infected infants were more likely to be single (odds ratio (OR) = 3.05, p = 0.016), to work in sales (OR = 4.93, p = 0.008), or to be students (OR = 5.01, p = 0.017). Conversely, women who worked in health-care professions were less likely to have a congenitally infected infant (OR = 0.14, p = 0.049). PCR analysis indicated 27 distinct strains of CMV, but two groups of infants (two infants per group) excreted strains with indistinguishable molecular patterns. One of these pairs of infants had older siblings who attended the same child-care center during their mothers' pregnancies. The authors concluded that demographic and occupational factors influenced the risk of giving birth to an infant with congenital CMV infection. Many distinct CMV strains were identified, suggesting that major point source outbreaks had not occurred. Nonetheless, point source acquisition of CMV from child-care environments did account for some cases of congenital CMV infection in eastern Iowa.