Our purpose was to determine if there is an association between nonalcoholic fatty liver and spleen enlargement. Spleen volume was measured by computed tomography (CT) in 32 patients with nonalcoholic fatty liver (23 men and 9 women; age, 41.6+/-12.1, range, 22-69 years) and 34 patients with normal liver (19 men and 15 women; age, 51.1+/-16.2, range, 14-86 years). The values were compared with the patient's demographic data, the liver-to-spleen (L/S) ratio of CT Hounsefield unit measurements, and the results of liver function tests. Diagnosis of fatty liver was made if the L/S ratio was less than 1.0. The mean spleen volume was 73.0+/-24.4 cm3 (range, 21.1-106.1) in normal subjects and 141.2+/-54.1 cm3 (range, 44.1-267.3) in patients with fatty liver (P<0.0001). Multivariate linear regression analysis identified that only the L/S ratio (P<0.0001) and age (P<0.01) were significantly correlated with spleen volume. Using forward selection stepwise regression, the L/S ratio entered first (beta = -0.634) and age second (beta = -0.293). In conclusion, spleen enlargement was commonly seen in patients with nonalcoholic fatty liver, and the recognition of this association may halt further attempts to evaluate the cause of spleen enlargement.