AIM: Knowledge of liver volume is needed in the preoperative screening of liver transplant donors and in pharmacokinetic studies. In previous studies, bodyweight, surface area, age and sex have been identified as predictors of total liver volume, but the impact of non-alcoholic fatty liver disease (NAFLD) independent of body size on liver volume has not been determined. We examined whether and to what extent liver fat due to NAFLD influences liver volume. METHODS: We quantified the percentage of liver fat by proton magnetic resonance spectroscopy ((1) H-MRS) and liver total, lean and fat volumes using magnetic resonance imaging (MRI) in 112 subjects (62 women, 50 men), who were characterized with respect to metabolic parameters associated with NAFLD. RESULTS: Of the subjects, 45% had NAFLD (liver fat 12.5 +/- 4.5% vs 1.8 +/- 1.6%, NAFLD vs no NAFLD, P < 0.001). Total liver volume was 29% higher in subjects with NAFLD (1.91 +/- 0.45 L) than in those with no NAFLD (1.49 +/- 0.31 L, P < 0.001). In multiple linear regression analysis, the percentage of liver fat and bodyweight independently explained variation in total liver volume (r(2) = 0.42, P < 0.001). The r-values for the relationship between metabolic parameters and the total liver fat volume were not significantly better than those between metabolic parameters and the percentage of liver fat. CONCLUSION: Both bodyweight and NAFLD increase liver volume independent of each other. Measurement of liver fat by (1) H-MRS allows accurate quantification of NAFLD and calculation of total liver volume.