Meconium aspiration syndrome occurs more commonly in infants subjected to fetal distress. The baboon model was utilized to produce in utero aspiration of meconium in the presence of fetal acidosis. Fifteen fetal baboons underwent acute catheterization of the femoral artery and a Swan-Ganz balloon was placed in the maternal aorta. Meconium was added to the amniotic fluid and the balloon was repetitively inflated to produce hypoxemia in 3 fetuses and hypoxemia and acidosis in 4. Two fetuses served as controls and the balloon was not inflated. Acidosis alone was produced in 3 others by maternal cooling. Maternal administration of fentanyl, a narcotic analgesic and respiratory depressant drug, was found to reduce the degree of in utero meconium aspiration in 3 distressed fetuses by inhibiting gasping respirations. It is concluded that fetal respiratory depressants may be useful in this circumstance but only when expert resuscitative capability is present in the delivery room.