Pulsatile luteinizing hormone (LH) secretion is suppressed by food restriction and rapidly restored by return to ad libitum feeding concomitant with an increase in the oxidation of free fatty acids, but no increase in plasma leptin concentrations or body fat content in ovariectomized ewes . The ingestion of food may stimulate LH secretion by increasing availability of oxidizable metabolic substrates. Ruminal digestion is characterized by the production of volatile fatty acids, and of these, propionate is the major gluconeogenic substrate, and both glucose and propionate are oxidizable in a variety of tissues. To examine whether increases in mesenteric propionate concentrations are sufficient for restoration of pulsatile LH secretion during a period of food restriction, adult, food-restricted, hypogonadotropic, ovariectomized ewes received mesenteric vein infusions of 5 mumol/ min/ kg body weight propionate or saline, while normal weight, ad libitum-fed ewes received mesenteric infusions of saline for 10 days. Blood samples were taken every 10 min for 5 h before the start of the 10-day infusion period, and continued throughout the first 5 h of infusion on the afternoon of Day 1, and in the morning on Days 2, 7 and 10. Propionate-infused, food-restricted (FR) and ad libitum-fed, saline-infused ewes showed a significantly higher LH pulse frequency compared to that of FR-saline-infused ewes on postinfusion Days 1 and 2 but not on Days 7 and 10, and only the saline-infused, FR group lost a significant amount of body weight. These results indicate that the reproductive system can respond acutely to infusion of metabolic fuels such as propionate, but sustained recovery of pulsatile LH secretion requires more than an increase in this single metabolic substrate.