Numerous authors have correlated the deposition of creatinine in amniotic fluid with advancing gestation, although the mechanism of creatinine transport is less well defined. This study was undertaken, therefore, to elucidate the route of creatinine exchange in the maternal- fetal complex by injection of creatinine- 1-C14hydrochloridc into the maternal and fetal compartments of canines and subhuman primates in the final trimester of pregnancy. The results suggest that in dogs and monkeys creatininc traverses the placenta in both directions, and that the sequence, maternal serum &OV0142; fetal scrum &OV0142; fetal urine &OV0142; amniotic fluid, is physiologically constant as long as normal circulator)' dynamics are maintained. The finding of labeled creatinine in the amniotic fluid of ncphreclomized canine fetuses was viewed with considerable interest as an indication of an alternate route of creatinine transport in the dog.