The ultrastructure of regenerating rat liver was studied during the first 4 days after two-thirds partial hepatectomy. It was found that changes occurred rapidly in cytoplasmic fat concentration and that there was pinocytosis of fat granules from plasma, with transport through cisternae of the endoplasmic reticulum and concentration in Golgi vacuoles. The number and electron density of cytosomes increased, and some of the electron density appeared to be lipid which came from Golgi vacuoles. Many of these changes disappeared by 9 hours after hepatectomy. Other non-specific changes, which consisted in swelling and pallor of mitochondria, loss of mitochondrialdense bodies, and wrapping of ergastoplasmic membranes about mitochondria, were observed. There was rapid increase in small granule content of the nucleus, both in the nucleolus and extranucleolar chromatin, beginning at 4 hours and reaching a maximum about 1 day after hepatectomy. These changes rapidly subsided so that, by 4 days after hepatectomy, most liver cells were normal except for decreased glycogen and the presence of cytoplasmic fat in occasional cells. This relative ultrastructural normalcy was somewhat surprising in view of the active proliferation of liver cells for 7–10 days after partial hepatectomy. The finding of striking ultrastructural changes in liver during the first few hours after hepatectomy suggests that investigation of the biochemical and biologic parameters of regeneration soon after hepatectomy might be particularly fruitful. Also, since the ultrastructural changes occur within the first few hours after hepatectomy, the occurrence of a specific circulating stimulus or inhibitor of regeneration would appear unlikely because a long period of time would seem to be required for sufficient change in their concentration to initiate regeneration.