The nationwide neonatal screening of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Taiwan was started on July 1, 1987. The effective collection rate has reached more than 96% of all newborns since 1993 and the overall incidence rate of G6PD deficiency was about 2%. This screening program has 3 screening centers and 18 referral hospitals, distributed around Taiwan including outlying islands. To assess the reliability of the confirmatory and screening tests, an external quality assurance (QA) program for G6PD assay was developed. For quantitative assay of G6PD activity, lyophilized quality control materials with different G6PD activities were prepared from red blood cells. For G6PD screening, quality control materials with different G6PD activities were prepared from whole blood and spotted onto the blood collecting filter paper. Periodically (1-2 months), the QC materials were sent to each of the referral hospitals and screening centers by speed post delivery. The external QA results were evaluated and compared to the median of all the reports and the reference values determined by our laboratory. Whenever an analytical system error was detected in any participating laboratory, troubleshooting was carried out either by contacting by phone or visiting in person. Twenty-one referral laboratories and 8 screening centers (3 in Taiwan, 2 in Mainland China, and one each in the Philippines, Thailand and Lebanon) participated in the QA program. Three to 5 QC specimens were sent to every participating referral laboratory for each quantitative survey. From January 1988 to June 2001, 104 QA surveys were carried out and 1,891 reports were received. Two hundred and thirty-nine (12.6%, 239/1,891) QA reports had abnormal results, attributed to clerical (13%, 31/239), experimental (17.2%, 41/239), and instrumental errors (46.4%, 111/239). Most of the experimental and instrumental errors were found in those laboratories that did not execute internal QA properly. For the screening QA program, 10 QC blood spots were delivered to every participating screening center for each survey. From March 1999 to June 2001, 15 screening surveys were performed with 111 reports received. One false negative (1/1,110) and 14 (14/1,110) false positive results were found in four (3.6%, 4/111) of the screening QA reports. The external quality assurance program proved useful for monitoring the performance of G6PD tests in referral hospitals and screening centers, and provided guidance for correcting analytical errors.