During a 72 hour fast in pregnant women, significant decrements in the maternal plasma glucose concentrations, accompanied by a significant increase in the plasma placental lactogen (hPL) concentration, occur. At the same time, utilization of glucogenic amino acids, principally alanine, takes place. The mean postprandial glucose concentration in pregnancy is significantly lower than that of comparable nonpregnant women (70.5 +/- 1.7 versus 79.5 +/- 1.3 mg. per 100 ml., p less than 0.001). There appears to be a significant sparing effect on the maternal plasma glucose concentration during acute fasting which may be mediated through hPL. Concentrations of amniotic fluid and fetal plasma glucose from women undergoing fasting decrease in a manner parallel to that of the mother. Fasting provokes a mean rise in plasma hPL of 33.2 per cent over basal levels. This rise is still evident 72 hours after refeeding, after which it gradually returns to pretest concentrations. The infusion of alanine or arginine to pregnant women at the end of the fast produced increments in the peripheral maternal glucose concentration. The response was much greater with alanine than with arginine, demonstrating the increased gluconeogenic potential of this amino acid. The increment in human growth hormone (hGH) following alanine infusion was significantly greater than that observed after arginine administration. Hypoaminoacidemia was present in nonpregnant and pregnant women in response to fasting, but the decline was greater in pregnancy. Acute fasting in the first half of gestation appears to produce significant alterations in carbohydrate metabolism evidenced by profound hypoglycemia, hypoinsulinemia, and hypoaminoacidemia. This maternal deficit can be reflected in fetal substrate concentrations. The effect of these changes on fetal growth and development is speculative at this time.