Apolipoprotein (apo) B is an essential component for the assembly and secretion of lipoproteins. The current report examines apo B production using primary cultures of hepatocytes derived from rats 3 to 21 days after partial hepatectomy (PH) to determine the effects of liver regrowth on apo B. Studies indicate that hepatocytes stimulated by PH have a two-thirds reduction in net apo B production 3 to 7 days after surgery, which coincides with the period of maximum rate of liver regrowth. Both higher (apo BH)- and lower-molecular-weight (apo BL) apo B are synthesized and secreted after PH, indicating the presence of edited apo B mRNA in hepatocytes. Hepatocytes derived from PH rats are more sensitive to insulin inhibition of apo B secretion compared with controls, suggesting an enhanced effect of insulin on newly replicated hepatocytes. Epidermal growth factor (EGF), a key regulator of liver regrowth following PH, potentiates the inhibitory action of insulin on apo B secretion in control hepatocytes and those derived from rats 2 to 3 weeks after PH. However, the potentiating effect of EGF on insulin inhibition of apo B is not discernible in hepatocytes 3 to 7 days after PH. The short-term in vitro hormonal effects occurring even with decreased apo B production suggest that this pathway remains available following PH to balance lipoprotein secretion with lipid and energy requirements necessary for liver regeneration.