Data for 38 children perinatally exposed to human immunodeficiency virus (HIV) were evaluated to determine the impact of cytomegalovirus (CMV) infection on the course of perinatally acquired HIV infection. Thirteen children belonged to the P0 (indeterminate) group, one to the P1 (asymptomatic) group, and 24 to the P2 (symptomatic) group, per the classification of the Centers for Disease Control. Of the 24 children in the P2 group, 10 died. The mean follow-up time was 22.8 months for the 10 children who died and 16.3 months for the 13 children in the P0 group. Serial cultures of urine were performed for all 38 patients. CMV was isolated from seven of 10 children who died and from four of 14 children who survived (P less than .05). Only one of the 13 P0 children was culture-positive for CMV, as compared with 11 of 24 P2 children (P less than .05). All CMV-infected children continued to demonstrate CMV viruria in serial cultures. The mean age at the time of the first culture positive for CMV was 13 months. Microcephaly was present in 15 (65%) of 23 P2 children but in none of the P0 and P1 children (P less than .05). Eight of 11 CMV-infected children were microcephalic; seven of 12 children not infected with CMV were microcephalic (P greater than .05). These data suggest that the prevalence of active CMV infection is significantly higher in P2 children than in P0 and P1 children. In addition, there is a significant association between CMV infection and mortality among P2 children.