We studied the effects of pharmacologic agents on umbilical blood flow and umbilical-placental vascular resistance in 18 fetal lambs in utero. Three groups of drugs were identified: the first had no effect on umbilical blood flow or umbilical-placental vascular resistance; the second altered umbilical blood flow secondary to changes in heart rate and placental perfusion pressure, but did not change umbilical-placental vascular resistance; the third decreased umbilical blood flow and increased umbilical-placental vascular resistance. The studies suggest mechanisms by which umbilical blood flow is regulated in the fetal lamb.