We analyzed national surveillance data that had been reported to the Centers for Disease Control and Prevention to elucidate the impact of recent clinical and public health efforts to further decrease the number of human immunodeficiency virus (HIV) infections and resulting morbidity caused by perinatal transmission. Long-term trends in pediatric (ages, 0-13 years), perinatal acquired immune deficiency syndrome (AIDS) cases were analyzed by log-linear Poisson regression for the period 1992-2004. Estimates for the number of perinatal HIV infections that occurred during the more recent period of 2001-2004 were developed by extrapolation from the 33 states with ongoing HIV (non-AIDS) reporting to the entire United States with the use of a probabilistic model. The number of pediatric perinatal AIDS cases that were identified decreased from 858 in 1992 to only 41 in 2004. These declines were consistent across demographic and regional subgroups. Data on the number of perinatal HIV infections suggests ongoing declines throughout the early years of the 21st century from 277 (95% CI, 224-346) in 2001 to 138 (95% CI, 96-186) in 2004. The incidence and morbidity associated with perinatal HIV infection continue to decline. To ensure that existing prevention efforts continue to achieve control of these infections, consistent methods of public health surveillance must be instituted throughout the entire United States.