A rapid assay for detection of cytomegalovirus (CMV) in saliva was evaluated as a screening method for congenital infection. Samples of saliva were examined by detection of early antigen fluorescent foci (DEAFF) and standard tissue culture (TC). Results were compared with those from urine DEAFF. CMV was detected in saliva from 31 (1.7%) of 1870 newborns, 26 by DEAFF and TC, 1 by DEAFF alone, and 4 by TC alone. Urine DEAFF was positive in 28 of these 31 newborns. The sensitivities of various tests were saliva TC, 96.8%; saliva DEAFF, 87.1 %; and urine DEAFF, 90.3%. A change in transport medium for 825 saliva samples resulted in improved sensitivities: saliva TC and saliva DEAFF, 100%; urine DEAFF, 92.3%. Screening saliva of newborns for CMV appears to be at least as sensitive a method for detecting congenital infection as detection of viruria; saliva can be collected with less difficulty and expense than urine. © 1993 by The University of Chicago.