The characteristics of the digestive and hepatic metabolism of glucogenic and ketogenic substrates were studied in vivo in fed or starved rats. For this purpose, a procedure for blood flow measurements in the splanchnic area was developed, based on an indicator-dilution technique. Hepatic blood flow (HBF) was markedly reduced after 24 h starvation, mainly corresponding to the decrease of portal blood supply; however, HBF expressed per gram liver was almost unchanged. In overnight-fed rats, glucose absorption was limited and glucose was released by the liver, essentially after gluconeogenesis from C3 units: alanine was the main glucogenic substrate removed by the liver, then propionate and lactate, whereas only a slight release of pyruvate occurred. As large amounts of lactate were released by the digestive tract, there was a net production of lactate in the splanchnic area. In contrast, in starved rats, lactate became the main glucogenic substrate removed by the liver as its fractional extraction was raised from 7% (fed) to 58% (starved) whereas the contribution of alanine and propionate to gluconeogenesis was limited by their availability, their hepatic extraction being highly efficient in fed and in starved rats. The present results are consistent with the view that glucose turnover was practically halved during starvation and suggest that net glucose cycling via lactate was very low in fed rats but could correspond to about 40% of produced glucose in starved rats. Besides propionate, acetate and butyrate made a significant contribution to fuel supply for hepatic metabolism in fed rats, acetate availability for extrasplanchnic tissues remained relatively constant. FFA were extensively removed by the liver (50%) in starved rats and ketogenesis could account for 68 % of removed FFA. In spite of low concentrations in the artery, acetoacetate was released by the liver at a higher rate than 3-hydroxybutyrate. This process could correspond to a higher turnover rate for acetoacetate, nevertheless not evident in portal-drained viscera where net 3-hydroxybutyrate uptake was observed only.