We used the minimal model technique to obtain concurrent measurements of whole-body insulin sensitivity and pancreatic B-cell responsiveness to glucose during the third trimester of pregnancy. Insulin sensitivity in normal pregnant women (n = 8) was reduced to only one third that of a group of nonpregnant women (n = 7) of similar age and relative weight. This marked insulin resistance was compensated by reciprocal enhancement of the first and second-phase insulin responses to intravenous glucose, which were increased threefold as compared with the nonpregnant women. Women with gestational diabetes mellitus (n = 16) had mean insulin sensitivity that was similar to that of the normal pregnant group, which indicates that insulin action was appropriate for the late phase of pregnancy in the gestational diabetic group. By contrast, the mean first-phase insulin response was significantly reduced in women with gestational diabetes mellitus, as compared with that of normal pregnant women (p less than 0.001). However, approximately one fifth of the group with gestational diabetes mellitus had first-phase responses that did not fall below the 95% confidence interval for the mean in normal pregnant women. The mean second-phase response was also lower in the group with gestational diabetes, although the difference was of borderline statistical significance (p less than 0.09). Our findings reveal the quantitative nature of the reciprocal changes in insulin sensitivity and B-cell function that normally accompany late pregnancy. They further indicate that during the third trimester, mild gestational diabetes is characterized by an impairment of pancreatic B-cell function rather than an exaggeration of the normal insulin resistance of late pregnancy.