Rates of plasma acetoacetate and total ketone-body production and oxidation to CO2 were determined by an isotope tracer technique in eight obese subjects undergoing progressive starvation. After a brief fast and under conditions of mild ketonemia and minimal ketonuria, rates of acetoacetate and total ketone-body production and oxidation were directly related to the increasing plasma concentration. After a longer fast and with severer ketonemia, acetoacetate and total ketone-body production and oxidation rates were higher but became constant and unrelated to the plasma concentrations. The maximum rates of total ketone-body production and oxidation were about 150 g/24 h and 129 g/24 h, respectively. Although an increased ketone-body production was the primary factor responsible for the hyperketonemia, an imbalance between production and removal of the ketone bodies cannot be excluded. Such an imbalance could account, at least in part, for the developing hyperketonemia and for the lack of relationship between production rates and plasma concentrations.