After experimentally inducing growth retardation by unilateral uterine artery ligation in midpreg-nancy, placental blood flow (PBF) (microsphere technique) and placental transfer of14C-aminoisobutyric acid (AIB) and3H-methylglucose (MG) were studied at d 44, 50, or 63 of gestation in 19 chronically catheterized awake guinea pigs. At d 44, fetal wt (FW) and placental wt were reduced by 16 and 18%, respectively, in the ligated horn and FW/ PBF was increased by 122%. Placental efficiency to transfer MG and AIB (fetal dpm/g placenta) was maintained in the ligated horn, feto-placental extraction (feto-placental dpm/PBF) was increased, and placental transfer of the substrate analogs (fetal dpm/g fetus) was unchanged. At d 50 and 63, placental wt and FW were reduced in proportion (∼40%) in the growth-retarded group and FW/PBF was increased by 80 and 51%, respectively. Placental transfer of AIB was reduced by 33% at d 50 and by 18% at d 63. In addition, placental efficiency to transfer AIB was reduced by 36% at d 50 and by 22% at d 63 in the growth-retarded group. Fetal uptake of MG per g fetus was slightly reduced (–6%) at d 50 of gestation, but unaffected at d 63. Extraction of MG from the maternal PBF was increased, whereas the wt-specific transfer capacity of the placenta was unaltered. Our results demonstrate that experimental growth retardation in the guinea pig is associated with a substantial reduction of FW-specific placental transfer of AIB, indicating that the growth-retarded fetus has an impaired supply of amino acids during intrauterine life. This reduction is suggested to be due to alterations at the placental barrier level and will contribute to the development of intrauterine growth retardation independently of the PBF decrease per se. Placental transfer of MG per g fetus was only moderately reduced at d 50 of gestation, but otherwise maintained. Consequently, compromised placental glucose transfer is not likely to be the main cause of fetal hypoglycemia in guinea pig intrauterine growth retardation.