Previous studies from our laboratory have shown that beta hydroxybutyrate crosses the ovine placenta in small amounts during maternal hyperketonemia and produces significant reductions in fetal PaO2 and increased fetal lactate levels. The present study evaluates the effects of fetal hyperketonemia on fetal and maternal cardiovascular and biochemical parameters. Pregnant ewes (110 to 120 days' gestation) were instrumented with catheters in the femoral artery, femoral vein, and uterine veins, and electromagnetic flow probes were placed on the middle uterine arteries. The fetal carotid artery and jugular vein were catheterized, and a catheter and balloon were placed in the amniotic fluid. Beta hydroxybutyrate (0.44 mmole/min) and antipyrine (0.03 mmole/min) were simultaneously infused directly into the fetal jugular vein for 90 minutes. The fetal beta hydroxybutyrate level increased from a baseline of 0.12 ± 0.08 to 6.80 ± 0.46 mmoles/L and was associated with a significant decrease in fetal PaO2 (23.7 ± 2.4 to 16.0 ± 0.4 mm Hg) and a large increase in the fetal lactate level (1.85 ± 0.27 to 5.43 ± 0.92 mmoles/L) at 90 minutes. The present results suggest that during fetal hyperketonemia fetal oxygenation is significantly reduced and may contribute to the increased perinatal mortality in the pregnant diabetic patient.