The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques. 2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation. 3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean +/- SE) 0.44 +/- 0.02 and 0.55 +/- 0.07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean +/- SE) 34 +/- 5 and 58 +/- 7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean +/- SE) 46 +/- 6 and 59 +/- 3% of the respective entry rates. 4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean +/- SE) 9 +/- 1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean +/- SE) 54 +/- 8% of the CO2 produced by the hind-limb being derived from NEFA oxidation. 5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb. 6. NEFA were not a significant energy source for the gravid uterus. 7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.
