The hypothesis that propionate is a short-term feed intake-regulating agent was studied. Mature wether sheep were infused over 20 min with Na propionate into the mesenteric vein, while feed intake and feeding pattern were monitored over 1.5 h. Feed intake was reduced by infusions at 2 mmol/min, which were associated with marked increases in jugular as well as portal concentrations of insulin, glucose, and propionate. In a second experiment, animals were infused with 2 mmol/min Na propionate into the portal vein. No decrease in feed intake was observed, although there were similar increases in insulin, glucose, and propionate as found in mesenteric vein-infused animals. It is concluded that mesenteric propionate in high doses acts as a satiety factor. Possible explanations for the difference between site of infusion may be a different distribution of the infusate over the liver and/or the presence of propionate-sensitive receptors in the mesenteric/portal vein region. It seems unlikely that insulin concentrations are involved in inducing satiety in propionate-infused animals.