1. The aim of this work was to investigate why non-lactating dairy cows are less susceptible to the development of ketonaemia during food deprivation than are dairy cows in early lactation. 2. The first experiment (Expt. A) consisted of determining the effect of 6 days of food deprivation on the concentrations of ketone bodies, and of metabolites related to the regulation of ketogenesis, in jugular blood and liver of non-lactating cows. 3. During the food deprivation, blood ketone-body concentrations rose significantly, but to a value that was only 16 % of that achieved in lactating cows deprived of food for 6 days [Baird, Heitzman & Hibbitt (1972) Biochem. J. 128, 1311Biochem. J. 128, -1318 ratio; a decrease in energy charge. These changes were all qualitatively similar to those previously observed in the livers of the food-deprived lactating cows. 5. There appeared therefore to be a discrepancy in the food-deprived non-lactating cows between the absence of marked ketonaemia and the occurrence of metabolic changes within the liver suggesting increased hepatic ketogenesis. This discrepancy was partially resolved in Expt. B by the observation in two catheterized non-lactating cows that, although there was a 2-fold increase in hepatic ketogenesis during 6 days of food deprivation, ketogenesis from the splanchnic bed as a whole (i.e. gut and liver combined) declined slightly owing to cessation of gut ketogenesis.Robertson et al. (1960) andBaird et al. (1972) demonstrated that mature cows that are in the early stages of lactation, i.e. about 25-50 days post partum, develop severe ketonaemia when deprived of food for 4-6 days. In more advanced lactation susceptibility to the induction of food-deprivation ketosis appeared to decline. These findings complement observations made by several authors that the susceptibility of lactating cows to spontaneous ketosis is greatest between 20 and 35 days post partum-and that uncomplicated spontaneous ketosis is rarely observed later than 75 days post partum (e.g. Halse & Mogstad, 1975).It seems therefore that the intensity of lactation may be a crucial factor in determining the susceptibility of non-pregnant cows to ketosis, since the lactational peak has been passed at 60-70 days post partum. It follows that non-lactating non-pregnant cows are likely to be particularly resistant to the induction of marked ketonaemia by means of food deprivation for short periods. *Present address: Biological Laboratory, University of Kent, Canterbury, Kent CT2 7NJ, U.K. Vol. 178Baird et al. (1972) found that the induction of ketosis in lactating cows by means of food deprivation was associated with major changes in the hepatic steady-state concentrations of a variety of metabolites, including intermediates of the tricarboxylic acid cycle and the Embden-Meyerhof pathway, ATP and NAD+. These changes were very similar to those previously found to be associated with spontaneous ketosis (Baird & Heitzman, 1971), and it was concluded that the changes in metabolite concentration, particularly the f...