The small-for-gestational age (SGA) infant resulting from intrauterine growth retardation (IUGR) is at high risk for perinatal complications and chronic morbidity. Most IUGR is the result of inadequate transfer of nutrients and/or oxygen from mother to fetus. Transamniotic fetal feeding (TAFF) has been proposed as a method of treating IUGR in which nutrients infused into the amniotic fluid would be swallowed, absorbed, and used by the growth retarded fetus. To study the efficacy of TAFF in the treatment of IUGR, we have previously described a rabbit model for TAFF that takes advantage of the relationship between "natural runting" (IUGR) and position on the uterine horn. We report on a controlled study of the effects of specific nutrient infusion on fetal growth retardation in this model. The infusion of dextrose, a dextrose-amino acid mixture, or lipid did not reverse or ameliorate fetal IUGR compared with controls. In addition, the infusion of lipid emulsion resulted in chronic lipid aspiration and further growth retardation. This work does not support the use of TAFF as a prenatal treatment for IUGR and suggests that oxygen may be the growth-limiting factor in most substrate deficiency IUGR. In addition, the infusion of solutions containing lipid may be harmful to the developing fetus.