Cytomegalovirus (CMV), the most common infectious cause of nervous system damage in the fetus and newborn infant, generally has been thought to exert its teratogenic effect during early pregnancy, and it has been assumed that clinical or postmortem abnormalities reflect static insults incurred earlier. Over the past two years we have identified two infants who presented with various clinical signs suggesting CMV infection. Serial CT head scans showed mild hydrocephalus progressing to extensive loss of brain substance and hydrocephalus in one and a normal scan going on to polycystic encephalomalacia in the other. Both infants had urine or leukocyte cultures that were repeatedly positive for CMV. These data suggest that CMV can cause progressive central nervous system damage after birth. The findings may account for some unexplained brain malformations and for a portion of the neurodegenerative disorders occurring in babies who appear normal at birth.