The glucose disappearance rate measured after IV glucose injection (1g/kg body wt) remained unchanged between 12 and 21 day of gestation in the rat. In contrast, insulin secretion in response to IV glucose was markedly increased on day 19 and 21 of pregnancy, suggesting resistance to endogenous insulin. Glucose kinetics (glucose production, utilization and clearance) in response to various doses of IV insulin have been studied in anaesthetised post-absorbtive 19 day pregnant and virgin rats using 6-(3)H glucose. With the supramaximal dose of insulin (4 U/kg body wt) no differences in glucose kinetics were found between pregnant and virgin rats. In contrast, with the two lower doses of insulin (0.15 and 0.05 U/kg body wt) glucose production was inhibited by 36 plus or minus 3% and 13 plus or minus 2% (Mean plus or minus SEM) respectively in virgin rats, but was not decreased in pregnant rats. When the effect of insulin on glucose clearance was expressed as % of the maximal effect obtained with 4 U/kg body weight, the rise in glucose clearance in response to the two lower doses of insulin (0.15 and 0.05 U/kg body wt) was lower in pregnant (57.5 plus or minus 6 and 27. 4 plus or minus 4%) than in virgin rats (73.3 plus or minus 6 and 42.2 plus or minus 7%). These results suggest that a decreased sensitivity to insulin appears in late pregnancy in the rat and could involve both liver and skeletal muscle.