Continuous infusions of [14C]glucose and [14C]lactate on separate days, and measurements of blood flow-rate, were used to obtain values for rates of unidirectional metabolism and of interconversion of glucose and lactate in the portal-drained viscera, liver and hind-quarters of ewes during late pregnancy and early lactation. All infusions were made within 5 h after the morning meal, when steady-state conditions appeared to exist. Use was made of ewes that had been appropriately catheterized during pregnancy, and whose catheters remained patent through into lactation. The liver was the main source of glucose production (67-70%) during both pregnancy and lactation. Other sources were the portal-drained viscera (absorbed glucose) and, presumably, the kidneys. Over 80% of the glucose was utilized by the peripheral tissues with approximately 35-40% of utilization being attributable to the hind-quarters. Of the total lactate production, 76% occurred in the peripheral tissues during pregnancy but only 36% during lactation. While the liver utilized 73% of lactate during pregnancy, this value fell to only 42% during lactation, at which time the portal-drained viscera utilized 26% of the lactate. During pregnancy, approximately 80% of the lactate arose from glucose, chiefly in peripheral tissues, while at least 12% of the glucose arose from lactate, chiefly in the liver. During lactation the extent of these interconversions was decreased. Despite the interconversions, whole-body turnover rates for glucose and lactate were under- or overestimated by only 4-10% and 2-5% respectively. Furthermore, a comparison of turnover rates obtained with [U-14C]- and [6-3H]glucose indicated that there was only 6 and 2% recycling of glucose-C during pregnancy and lactation respectively. Under the conditions employed in this study, lactate does not appear to be a major precursor of glucose in the ruminant, and most of the lactate taken up by the liver must be used for purposes other than gluconeogenesis, such as oxidation or alternative anabolic pathways.