The effects of age and caloric restriction on cell proliferation, measured as scheduled DNA synthesis (SDS), were evaluated in primary hepatocyte cultures from control and partially hepatectomized (PH) young to old ad libitum (AL) and caloric-restricted (CR) male Fischer 344 (F344) rats. We reported significant age- or CR-related decreases in SDS in control cultures. PH-induced cultures exhibited significant increases in SDS compared with their control counterparts. Hepatocytes from PH-induced old CR diet-fed animals exhibited significant increases in SDS compared with cultures from control old CR, PH-induced young CR and PH-induced old AL animals. Alternatively, SDS rates for PH-induced young CR animals were significantly lower at 48 h and higher at 72 h than the rates we reported for cultures from PH-induced young AL F344 rats. These data suggest that CR decreases and preserves the proliferative capacity in hepatocytes from young animals and may permit animals to respond more efficiently with induced compensatory cellular replication in old age.