This study was undertaken to determine how, and where, 2-hydroxy-4-methylthiobutyrate (HMTBA) can augment Met metabolism in lambs. Four lambs (initial body weight of 50kg, SE = 2, and 6 mo of age) prepared with catheters in the mesenteric, portal, hepatic, and jugular veins plus the aorta, were fed at 1.5× maintenance on a grass hay, barley, fish meal, molasses/pre-mix (5:3:1:1, as fed) diet, supplied as hourly meals. Lambs were infused for 10h with [methyl- 2 H 3 ]Met (0.11 mmol/h) in a jugular vein and p-aminohippurate into the mesenteric vein. From 1h onwards, successive 3-h infusions of saline (control), 0.55 mg/min (3.67μmol/min), and 4.44 mg/min (29.6μmol/min) of HMTBA were also infused into the mesenteric vein. Plasma, sampled continuously, was collected every 20min during the last 60min of each infusion. All infused HMTBA was recovered at the portal vein with 25% extracted subsequently by the liver. Portal appearance of total Cys and Met was unaltered by HMTBA infusion, but net splanchnic appearance of Cys increased (0.04, 0.08, 0.23 mmol/h, SEM = 0.05), whereas Met decreased (0.14, −0.01, −0.21 mmol/h, SED = 0.05). Despite this, arterial Met increased (27.0, 30.7, 51.5μM, SEM = 2.1) as did Met irreversible loss rate (27.6, 28.7, 40.1μmol/h, SEM = 0.51), equivalent to 40% of the HMTBA reentering the plasma after conversion to Met. These data indicate that, in ruminants, HMTBA is probably converted to Met within peripheral tissues; that is, where the metabolic need for Met exists.