Changes in visceral organ mass and hepatocyte metabolic activity in response to nutrient deprivation were studied in male Sprague-Dawley rats. Forty-two rats (320 g) were given ad libitum access to feed or fasted for 72 h after which time visceral organ mass and metabolic activity were measured. Liver metabolic activity was measured in vitro by [14C]valine incorporation into acid-precipitable protein and oxygen consumption in isolated hepatocytes. Fasted rats had lower weights of liver and intestines and similar kidney and stomach weights relative to body weight than fed rats. Compared with fed controls, fasted rats had lower RNA and higher DNA concentrations in liver and intestines with decreased RNA and protein mass in all visceral organs. Nutrient deprivation generally resulted in reduced ratios of RNA/DNA and protein/DNA in visceral tissues. Nutrient deprivation had no effect on in vitro oxygen consumption or [14C]valine incorporation expressed per g tissue. However, in vitro oxygen consumption and valine incorporation expressed per unit DNA and estimated total liver oxygen consumption were reduced in fasted rats. These data suggest that nutrient deprivation reduced visceral organ mass of RNA and protein primarily through an apparent reduction in cell size. Nutrient deprivation resulted in decreased liver oxygen consumption because of decreased organ size rather than by tissue metabolic activity.