The accuracy of the Continuous Glucose Monitoring System, CGMS (Medtronic MiniMed, Northridge, CA) was assessed in children and adolescents with type 1 diabetes mellitus (T1DM) when compared with reference serum glucose levels during spontaneous fluctuations in glucose levels over 24 h and during acute hyper- and hypoglycemia. Ninety-one subjects with type 1 diabetes (3.5-17.7 years old) wore one or two CGMSs while blood samples were obtained for serum glucose determinations (made at a central laboratory) hourly during the day, every 30 min overnight, and every 5 min during meal-induced hyperglycemia and insulin-induced hypoglycemia tests, resulting in 6778 CGMS-reference glucose pairs. CGMS function was assessed on each of the 3 days of sensor life. The median relative absolute difference (RAD) between the CGMS and reference values was 18% (25th, 75th percentiles = 8%, 34%). Similar results were obtained on each of the 3 days of sensor life. Accuracy was worse during hypoglycemia than during hyperglycemia. Modified sensors that first became available in November 2002 were more accurate than were the original sensors (median RAD = 11% vs. 19%) and had better precision (r = 0.92 vs. r = 0.77) during time periods in which two CGMSs were simultaneously used. The CGMS sensors that have been in clinical use until recently are often inaccurate in quantifying glucose values in children with T1DM. However, recent modifications to the sensor have resulted in substantially better accuracy and reliability. This improved function, if confirmed by additional data, may enhance the clinical utility of the CGMS.