The epidermal growth factor receptor shows acinar heterogeneity with a portal-to-central concentration gradient. Immunohistochemical analysis showed that the strong cytoplasmic staining for epidermal growth factor receptor found in normal hepatocytes disappears over time after partial hepatectomy or sham operation, however, with different time courses. Four hours after surgery, 84.3 +/- 3.5% (mean +/- SD) of the hepatocytes in animals after sham operation showed strong cytoplasmic staining vs. 21.8 +/- 19.0% in animals after partial hepatectomy. After 12 h, the cytoplasmic staining in animals after sham operation was further reduced to 39.0 +/- 22.6% vs. 20.0 +/- 5.5% in animals after partial hepatectomy. At the same time point, we found staining for the epidermal growth factor receptor in nuclei of 21.8 +/- 14.8% and 3.0 +/- 3.9% of the hepatocytes in animals after partial hepatectomy and animals after sham operation, respectively. Northern blot analysis revealed comparable changes in expression of the epidermal growth factor receptor mRNA in animals after partial hepatectomy and in animals after sham operation. No changes were evident in animals after sham operation, however, if the abdominal incisions were shortened. This suggests that at least part of the changes found in animals with sham operation are due to acute phase events and/or surgical stress. In conclusion, partial hepatectomy induces changes in the intracellular and acinar fate of the epidermal growth factor receptor, drives the receptor to the nuclei, and affects the expression of the epidermal growth factor receptor mRNA.