The current studies were performed to better understand the physiological relevance of acetate in the poorly ketogenic piglet and to determine if endogenous acetogenesis rises with increased mitochondrial fatty acid -oxidation, analogous to ketogenesis. Plasma acetate concentration values in newborn, fasted, or suckled piglets (230-343 µM) were at least 10-fold higher than the ketone bodies, a pattern opposite to that in 24- to 48-h suckled rats (77-175 µM). Employing continuous infusion techniques with sodium [³H]acetate tracer in fasting ~40-h-old piglets, acetate rate of appearance (R_a) was found to be 34 ± 4 µmol · min¹ · kg body wt¹. This basal R_a was double that observed in animals coinfused with sodium [1-¹⁴C]hexanoate (P < 0.001), despite active oxidation of the latter as determined by ¹⁴CO₂ production. Active acetogenesis in vivo and relatively abundant acetate in piglet blood are consistent with the hypothesis that acetate plays an important physiological role in piglets. However, the negative impact of hexanoate oxidation upon acetate R_a and the lack of significant changes in circulating acetate in newborn, suckled, and fasted piglets draws into question the extent of analogy between acetogenesis and ketogenesis in vivo.