Magnetic resonance spectra from large (35 cm3) frontal lobe voxels in vivo were analyzed using LCModel, with and without subtraction of a "metabolite nulled" spectrum with an inversion time of 650 ms to characterize the macromolecule baseline. Baseline subtraction decreased the signal to noise ratio (SNR), but improved the reliability of LCModel quantification of most metabolites, as reflected in the Cramer-Rao lower bounds, in particular for glutamate and glutamine. The reported concentrations increased for glutamine, creatine, and lactate, and decreased for glutamate, myo-inositol and NAAG, but the sum of all metabolites remained constant, as did the standard deviation of the concentrations in the control group. Macromolecule subtraction is worthwhile when SNR is high, as in the characterization of normal-appearing tissue in the brain.