To determine whether insulin resistance exists in maternal skeletal muscle during pregnancy and how it returns to normal during the postpartum period, 3-O-methyl[14C]-D-glucose transport and [125I]insulin-binding activities were measured in isolated rat epitrochlearis muscle. Maximally insulin-stimulated methylglucose transport activity was decreased on day 20 of pregnancy and on days 1 and 4 post partum; it returned to the nonpregnant level by day 9. The insulin-binding activity did not change significantly throughout pregnancy, increased on days 1 and 4 post partum, and returned to the nonpregnant level by day 9. There was no significant difference in insulin binding or insulin-stimulated methylglucose transport activity between lactating and nonlactating animals. These results suggest that insulin resistance caused by postbinding changes in epitrochlearis muscle develops during late pregnancy and continues at least until day 4 post partum. Lactation does not appear to have a significant effect on insulin resistance.