In February 1999, Massachusetts introduced expanded newborn screening for 20 rare metabolic disorders by MS/MS. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) was mandated, in addition to 9 previously screened disorders, while the remaining 19 were offered as an optional pilot. Approximately 98% of parents have elected to participate in the optional program. Maine added MCAD in September 1999, and the optional disorders in July 2001. The other New England states are currently studying the benefits of adding additional testing. Expanded MS/MS screening in Massachusetts has thus far yielded a prevalence of approximately 1: 10,000 [200,000 screened--22 total cases--MCAD (7), VLCAD (1), SCAD (5), PA (2), 3-MCC (1), citrullinemia (1), ASA (1), argininemia (1), CPT11 (1) and 2 patients (argininemia and CPT11) with a severe neonatal presentation who died in the immediate newborn period]. All surviving patients have normal developmental outcomes so far. To evaluate the benefit of expanded newborn screening in the New England Region, the New England Consortium of Metabolic Centers has undertaken a prospective 3 year study, comparing the outcomes of patients identified by MS/MS with those diagnosed clinically. To date 22 screened patients (10 MCAD, 4 SCAD, 1 VLCAD, 1 CPT11, 13-MCC, 2 PA, 1 ASA, 1 citrullinemia and 1 argininemia) have been enrolled along with 24 clinically identified patients (7 MCAD, 1 SCAD, 1 VLCAD, 1 LCHAD, 1 argininemia, 1 tyrosinemia type 1, 6 PA, 3 GA 1, 2 GA 11, 1 MMA). Studies include: medical exam, neuropsychological assessment (Bayley Test and Stanford-Binet Test of Intelligence) and medical record review. Preliminary data suggest that the screened patients have an improved clinical outcome with fewer hospitalizations and so far, no neurological complications.