ABSTRACT: We developed extraction and analysis protocols for element detection in neonatal blood spots (NBSs) using sector-field inductively coupled plasma-mass spectrometry (SF-ICP-MS). A 5% (v/v) nitric acid element extraction protocol was optimized and used to simultaneously measure 28 elements in NBS card filter paper and 150 NBSs. NBS element concentrations were corrected for filter paper background contributions estimated from measurements in samples obtained from either unspotted or spotted NBS cards. A lower 95% uncertainty limit (UL) that accounted for ICP-MS method, filter paper element concentration, and element recovery uncertainties was calculated by standard methods for each individual's NBS element concentration. Filter paper median element levels were highly variable within and between lots for most elements. After accounting for measurement uncertainties, 11 elements (Ca, Cs, Cu, Fe, K, Mg, Na, P, Rb, S, and Zn) had lower 95% ULs>0?ng/spot with estimated concentrations ranging from 0.05 to >50,000?ng/spot in ?50% of NBS samples in both correction methods. In a NBS sample minority, Li, Cd, Cs, Cr, Ni, Mo, and Pb had estimated concentrations ?20-fold higher than the respective median level. Taking measurement uncertainties into account, this assay could be used for semiquantitative newborn blood element measurement and for the detection of individuals exposed to supraphysiologic levels of some trace elements. Adequate control of filter paper element contributions remains the primary obstacle to fully quantitative element measurement in newborn blood using NBSs.