Little is known about the relation between liver regeneration and splenic size. We monitored serial changes in liver and spleen volumes using computed tomography in 24 patients with biliary cancer who underwent right hepatectomy or more extensive liver resection following portal vein embolization (PVE). Nonembolized hepatic segments increased in volume from 316 +/- 97 cm3 (34% +/- 8% of total liver volume) before PVE to 410 +/- 115 cm3 (44% +/- 8%) after PVE. The volume of nonembolized hepatic segments (i.e., remnant liver) increased to 617 +/- 111 cm3 (59% +/- 10% of total liver volume before PVE) 14 days after hepatectomy and then increased slowly to reach 795 +/- 231 cm3 (76% +/- 16%) 1 year after hepatectomy. Splenic volume increased from 87 +/- 29 cm3 before PVE to 104 +/- 38 cm3 (119% +/- 17% of original volume) after PVE. Splenic volume increased to 137 +/- 65 cm3 (155% +/- 40%) by 14 days after hepatectomy and to 155 +/- 67 cm3 (179% +/- 41%) by 28 days after hepatectomy, with no further change at 1 year after hepatectomy (153 +/- 92 cm3; 174% +/- 79%). The rate of increase in splenic volume within the first 14 days after hepatectomy was 2.7 +/- 3.6 cm3/day, correlating well with increases in remnant liver volume ( r = 0.64, p = 0.0006). These data indicate that the spleen is enlarged during liver regeneration, suggesting that the liver and spleen share certain common growth regulatory mechanisms.