Kupffer cells contribute to the pathogenesis of liver injury in chronic liver disease, yet it is difficult to assess Kupffer cell function either ex vivo or in vivo, since supporting data are limited. The aim of this study was to clarify the relation between Kupffer cell function and hepatocyte function by analyzing the correlation between conventional indices of hepatic functional reserve and both superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) and technetium-99m-galactosyl human serum albumin scintigraphy (Tc-99m-GSA) in patients with chronic viral hepatitis. Consecutive 46 patients (16 patients with chronic hepatitis and 30 patients with cirrhosis) who underwent both SPIO-MRI and Tc-99m-GSA were examined. The patients were aged 46-83 years (median 70) and included 29 men and 17 women. Spearman correlation coefficient was used to analyze the correlations between functional reserve indices and both reduction percentages of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of Kupffer cell function and Tc-99m-GSA parameters. The usefulness of each parameter as a marker to differentiate Child-Pugh A from Child-Pugh B/C was evaluated using receiver operating characteristic (ROC) analysis. The reduction-%LMR correlated more closely with Child-Pugh score (r=0.77; P<0.001) than did Tc-99m-GSA parameters. For predicting Child-Pugh B/C, ROC analysis revealed that reduction-%LMR (AUC=0.91, P<0.001) was the most useful parameter and at a cutoff value of 50% or less, sensitivity, specificity, positive and negative predictive values were 0.79, 0.91, 0.94 and 0.71, respectively. SPIO-MRI may be a helpful non-invasive method for the evaluation of hepatic functional reserve, and this study suggests that Kupffer cell function is closely correlated with hepatocyte function in patients with chronic viral hepatitis.