In nine 2- to 3-month-old hyperketonaemic piglets the kinetics of glucose and D-beta-hydroxybutyrate (D-BHB) metabolism were studied during hypo- and normocalcaemia in paired experiments. Hyperketonaemia (1.3 and 2.5 mmol D-BHB (l plasma)-1) was generated by a stepwise increase of DL-BHB infusion. Hypocalcaemia spontaneously developed in five piglets due to an inherited calcitriol deficiency and was induced in four control piglets by a continuous infusion of Na2-EDTA. The method of single isotopic marker injections of glucose and D-BHB was used to calculate replacement rates, rate constants and half-lives of glucose and D-BHB in plasma. When DL-BHB was infused at the same rate into normo- and hypocalcaemic piglets, hypocalcaemia reduced the rate constant of glucose by 20-30% and the replacement rate of glucose by 34%. In the presence of hyperketonaemia, hypocalcaemia increased the rate of replacement of D-BHB by 6-40%. The replacement rate represents the sum of endogenous production and the rate of DL-BHB infusion. This observation shows that the endogenous production of D-BHB was higher during hypocalcaemia than during normocalcaemia.