The use of Lorentzian model lineshapes leads to systematic errors in the quantification of in vivo (1)H NMR spectra. Experimental lineshapes are better modeled by the Voigt (mixed Lorentzian-Gaussian) function, leading to more accurate fits (reduced chi(2)). In this work, results from a group of 41 subjects are presented. It is shown that not only are the estimated metabolite peak areas affected by the choice of lineshape model, but so too are the metabolite ratios. For example, the NAA/choline ratio was 1.92 +/- 0.06 (mean +/- standard error) using the Lorentzian lineshape model and 1.85 +/- 0.05 using the Voigt lineshape model. The corresponding figures for NAA/creatine were 2.32 +/- 0.06 and 2. 10 +/- 0.05 respectively, which are significantly different for the two lineshape models. An explanation of this previously unreported effect is given. This finding clearly has serious implications for the methodology and reporting of spectroscopic studies.