Food deprivation during pregnancy leads to an increase in maternal and fetal prostaglandin (PG) production and increased uterine contractility. We investigated the effect of maintaining fetal normoglycemia during food withdrawal-induced maternal hypoglycemia on uterine 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) production and myometrial activity in late pregnant sheep. Pregnant sheep were surgically instrumented with fetal and maternal catheters and electromyogram leads under halothane anesthesia. Maternal and fetal blood plasma samples were obtained once a day at 0900 h, 24 h before (baseline sample) and after 48 h of food withdrawal. Food, but not water, was withdrawn from ewes in group I (n = 5). During food withdrawal in group II (n = 5), glucose was infused into a fetal vein to maintain fetal normoglycemia. All data were normalized to the concentration in the baseline sample in each animal as 100%. After 48 h of food withdrawal, maternal whole blood glucose fell by 42.2 +/- 4.4% (mean +/- SEM: group I) and 31.4 +/- 6.2% (group II). These values were not significantly different. Fetal blood glucose fell by 40.4 +/- 5.7% (group I). In group II, fetal blood glucose was maintained in the normal range (99.6 +/- 1.6% of baseline). Maternal uterine electromyogram activity, uterine venous estrone sulfate, and uterine veno-arterial difference in PGFM rose significantly during food withdrawal in group I ewes, but not in group II ewes. Maternal and fetal arterial plasma ACTH and cortisol did not change in group II animals. We conclude that maintenance of fetal normoglycemia during 48 h of food withdrawal in sheep prevents the increase in myometrial activity, maternal plasma estrogens, and uterine PGFM production during food withdrawal in late pregnancy.