Specific immunoglobulin M antibodies were detected by radioimmunoassay (RIA-IgM) in cord sera from 83/93 (89%) babies congenitally infected with cytomegalovirus (CMV) but in 0/104 cord sera from uninfected control subjects. The type of maternal infection did not affect the ability of the assay to identify congenital infections, but increased RIA-IgM titers were found more frequently in cord sera from babies infected following primary CMV infections (9/18; 50%) than following recurrent CMV infections (1/12; 8%) (P less than .05). The magnitude of the fetal immune response was related to disease inasmuch as 14/40 (35%) babies with increased RIA-IgM titers were symptomatic at birth compared with 1/43 (2%) with lower titers (P less than .001). When combined with the results of testing for rheumatoid factor and total IgM, the RIA-IgM assay defined subgroups of babies with generally poor (7/15; 47% symptomatic at any stage) or generally good (0/21 symptomatic) prognoses. Prospective studies currently identifying cases of congenital CMV infection may wish to use these three serologic techniques as the results obtained appear to have prognostic significance for those babies who are initially asymptomatic.