Whereas insulin secretion in response to IV glucose is markedly increased between day 17 and 21 of gestation in the Rat, glucose disappearance rate remains unchanged. This suggests that maternal tissues become less sensitive to endogenous insulin. Glucose kinetics (glucose production, utilization and clearance) in response to various doses of IV insulin have been studied in 19 day pregnant and virgin rats by using [6-3H] glucose. With a supramaximal dose of insulin (4 U/kg body wt) no difference was found between pregnant and virgin rats. In contrast, with the two inframaximal doses of insulin (0.15 & 0.05 U/kg) glucose production was not decreased in pregnant rats whereas it was inhibited by 36 and 13% in virgin rats. Moreover the increase in glucose clearance was higher in virgin (186 & 146 %) than in pregnant rats (160 & 124 %). This suggests that decreased sensitivity to insulin in late pregnancy involves both liver and peripheral tissues. In vitro, glucose transport and metabolism were stimulated to the same extent by insulin in soleus muscles of pregnant and virgin rats. This suggests that insulin resistance in pregnancy could result from circulating antagonists of insulin (FFA, progesterone, placental lactogen).