The c-myc proto-oncogene encodes a transcription factor that is involved in cell proliferation, growth, differentiation, and apoptosis. Previous studies on the regulation of hepatic c-myc have focused on control of its mRNA expression, which generally correlates with hepatocyte proliferation during both liver development and liver regeneration. However, Western blot analysis showed similar levels of hepatic c-Myc in fetal and adult liver. We therefore went on to examine the abundance and distribution of hepatic c-Myc. Immunofluorescence on adult rat liver cryosections showed that c-Myc was readily detectable, but that it was largely localized to the nucleolus. In contrast, proliferating fetal hepatocytes and adult hepatocytes from regenerating liver showed a diffuse nuclear pattern. Transient transfection of adult hepatocytes with full-length HA-Myc also revealed localization to the nucleolus. Western immunoblotting studies confirmed that immunoreactive c-Myc was present in nucleolar extracts isolated from adult liver. We speculate that the nucleolus may act to sequester c-Myc in quiescent hepatocytes while providing a pool of c-Myc that is readily available to reach its targets in the nucleus.