ABSTRACT— A quantitative analysis of the liver was performed at intervals of 24, 48, 72 and 96 h and 7, 21 and 50 days following total biliary obstruction (TBO) in the Sprague‐Dawley rat. During this period, the liver weight increased from 7.72±0.51 g (mean±SEM) in controls to 24.57±1.66 g (p<0.0005) at 50 days. There was a concomitant reduction in the volume proportion of the liver occupied by liver cells, from 71.37±1.36% to 21.54±3.27% (p<0.0005), but there were increases in the volume proportions of biliary epithelial cells (BEC) from 0.14±0.02% to 16.39±1.12% (p<0.0005), of other cell and tissue types from 5.50±4.89% to 30.73±2.42% (p<0.0005) and of vascular and biliary channel spaces from 22.99±1.17% to 31.35±0.87% (p<0.0025). In control animals, the liver cell and BEC volume was estimated to be 6240±360 μm3 and 100±10 μm3, respectively. Following TBO, the liver cell volume was significantly greater than control only from 48–96 h, whereas the BEC increased significantly in volume from 24 to 72 h and then remained approximately 6 times the control value until the end of the period of study. Contrary to the histological appearance and decrease observed in volume proportion, the total liver cell population did not significantly differ from the control value of 8.83 × 108±0.80 × 108 cells, other than at 21 days when it increased to 14.90 × 108±1.04 × 108 cells (p<0.05). When expressed as the number of liver cells/100 g b.wt., an increase from the control value of 4.37 × 108±0.32 × 108 cells was observed only at 7 (5.66 × 108±0.42 × 108 cells; p<0.05) and 21 days (6.94 × 108±0.48 × 108 cells; p<0.05). This maintenance of liver cell population, following biliary obstruction, at or above the control values matches the clinical observation of preserved liver cell function. The total BEC population in control livers was 1.11 × 108±0.20 × 108 cells. A significant increase in this population was observed at 7 days (3.82 × 108±0.62 × 108 cells; p<0.05) with further increases to 57.90 × 108±6.42 × 108 cells (p<0.05) at 50 days, 52 times the control value. When expressed as cells/100 g b.wt., similar changes were observed. The results reported here indicate the importance of taking into account the change in the entire organ size and total mass of the cells in question when assessing alterations in their number.