The glucose homeostasis in the infants of normal and diabetic mothers was elevated by examining the effects of exogenous glucose infusion at 4 mg/kg . min and quantifying the rats of glucose production and utilization. Five infants of insulin-dependent diabetic mothers (IDM), one infant of a gestationally diabetic mother and five infants of normal mothers were studied between 2-4 h of age. The rates of glucose production and utilization before and during glucose infusion were quantified by tracer dilution technique using [6,62H2] glucose tracer and gas chromatography-mass spectrometry. Fractional glucose uptake (Kt) was measured at the end of infusion by administering 0.5 g/kg glucose pulse. All diabetic women were under rigid metabolic control during pregnancy. Although basal plasma glucose levels at e 2-4 h were lower in the IDMs as compared with normal newborns (43.4 +/- 3.7 and 65.2 +/- 3.6 mg/dl, mean +/- S.E., respectively), the glucose production and utilization rates were not significantly different (3.35 +/- 0.26 and 3.39 +/- 0.08 mg/kg . min); therefore, the metabolic clearance rates were higher inthe IDMs (7.69 +/- 0.41 ml/kg . min) as compared with the normal newborn infant (5.20 +/- 0.20 ml/kg . min). Glucose infusion resulted in a greater suppression of endogenous glucose production rate in the normal newborn infants than in the IDMs. Glucose infusion resulted in an acceleration of Kt in the normals (2.38 +/- 0.25%/min). We conclude that rigid regulation of maternal diabetes normalizes glucose production rate in IDM; however, intermittent maternal hyperglycemia may result in altered regulation of hepatic glucose production.