To determine if sampling of arterialized-hand venous (HV) blood is a suitable alternative for arterial (A) blood to study ketone body metabolism, concentrations of unlabeled and labeled ketone bodies were measured during continuous infusion of 3-14C-acetoacetate in simultaneously drawn samples from A and HV blood in normal subjects. The mean difference of acetoacetate between A and HV blood was in the basal state 1.5% and that of beta-hydroxybutyrate 6% (n.s.). Similarly, the 14C-content of ketone bodies and their calculated rates of production of metabolic clearance were not significantly different between A and HV blood. Following induction of ketosis by acetoacetate loading infusions, the difference of concentrations and 14C-content of total ketone bodies between HV and A blood remained insignificant (average 3%), and ketone body kinetics calculated from A and HV blood were similar. Furthermore, concentrations of glucose, lactate and pCO2 did nit differ significantly between the two sampling sites. In contrast, concentrations of ketone bodies, glucose and pO2 were significantly lower, and the metabolic clearance rate of ketone bodies and pCO2 higher in antecubital venous blood compared to heated-hand venous blood. Thus, the similarity of heated-hand venous and arterial blood suggests that the noninvasive technique is suited for kinetic analyses using tracer methods and for arteriovenous balance studies of ketone bodies.