Homocysteine (Hcy) is an intermediary S-containing amino acid produced by the methylation process within all cells. It is known as a powerful pro-oxidant with multiple deleterious effects on immune and physiological functions. Blood plasma total Hcy (tHcy), the most common indicator of Hcy status, can be reduced by dietary folates or vitamin B(12) in pigs as in most mammalians. In humans, homocysteinemia is routinely assessed after an overnight fast (≥ 12 h) although information is not available on circadian tHcy changes. Using a subgroup of pigs from a study on portal appearance of vitamin B(12) after a single meal containing 0, 25 or 250 μg of cyanocobalamin, the present study aimed to report the circadian profile of postmeal blood plasma tHcy and estimate the contribution of portal drained viscera (PDV) to the systemic tHcy. Four pigs (39.7 ± 1.1 kg BW) were surgically equipped at 101.0 ± 8.2 d of age with catheters in the portal vein and carotid artery; an ultrasonic flow probe was also fitted around the portal vein for blood flow recordings. Blood samples were collected simultaneously from the 2 catheters once before meal and at least every hour during 24 h after ingestion of 1.2 kg of a vitamin-free semipurified diet. Arterial tHcy changed considerably during the 24-h postmeal period (P < 0.001; SE = 0.8). In fact, from 12.3 μM 10 min before meal, tHcy gradually reached a maximum of 23.4 μM 13 h postmeal and returned to 15.5 μM 23 h after the meal. Net fluxes of tHcy across PDV were not influenced by levels of dietary vitamin B(12), postprandial time, or their interaction (P > 0.25); average net flux did not differ from zero (P > 0.08). These results suggest that systemic Hcy following a meal originates from metabolic pools other than PDV. It appears that an overnight fast of 12 h will reflect the peak rather than the basal value for tHcy. The duration of the fasting period is therefore a critical factor for a reliable interpretation of tHcy homeostasis in pigs. Such information may be also relevant for human health and nutrition because pig is recognized as a reliable model for Hcy metabolism.