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Epidemiologic projects have been implemented for using dried-blood spot (DBS) specimens routinely collected on filter paper from neonates as a seroepidemiologic resource to monitor seroprevalence of human immunodeficiency virus (HIV) among childbearing women. To ensure the quality of the data base produced from the national and other epidemiologic surveys, a quality assurance program was developed to interact with all the neonatal screening laboratories. The focus of the Centers for Disease Control's quality assurance program for HIV seropositivity testing of neonatal blood specimens is to maintain a national program to produce, certify, and provide external quality control materials as DBSs on filter paper, to monitor the filter paper matrix, to operate an external performance surveillance program, and to provide other special and consultative services. The dried-blood control and surveillance materials are certified by rigorous testing for accuracy, stability, and homogeneity. Preliminary results from the first performance evaluation of screening laboratories indicated excellent performance.