Although glucose is an important fuel for fetal oxidative metabolism, regulation of its availability to the mammalian fetus is poorly understood. This study was performed to determine the effect of infusions of insulin into the uterine arterial circulation on umbilical uptake of glucose in chronically instrumented, unstressed sheep. Twenty-eight determinations of umbilical glucose uptake and diffusion clearance of glucose by the placenta were made in four ewes. Immediately following a control study during which saline was infused into the uterine artery, porcine regular insulin diluted in saline was infused at 0.05 to 8.1 mU/min . kg uterine weight for 20--30 min and the determinations were repeated. Subsequent studies were performed at the conclusion of additional infusions of insulin to a maximum of 21.6 mU/min . kg. There was a significant increase in umbilical glucose uptake during initial insulin infusions (4.47 +/- 0.6 mg/min . kg fetus) compared to the control studies (3.08 +/- 0.6 mg/min . kg) associated with an increase in diffusion clearance (13.8 +/- 1.9 ml/min . kg fetus vs. 8.99 +/- 1.8 ml/min . kg). When the total cumulative dose of exogenous insulin, It, was 162 mU/kg uterine weight or less, the umbilical uptake of glucose, Q, may be expressed as a function of maternal arterial blood glucose concentration in milligrams per dl, [A], and of It.