OBJECTIVE: To determine the effects of single or repeated intramuscular injections of betamethasone, given maternally or directly to the fetus, on chronically catheterized, late-gestation fetal sheep. METHODS: Fetal or maternal sheep received either repeated intramuscular injections of betamethasone (0.5 mg1kg body weight at 104, 111, and 118 days' gestation), single betamethasone injection (at 104 days' gestation, followed by saline at 111 and 118 days' gestation), or repeated saline injections; n = 6 or 7 per group. At approximately 130 days' gestation fetuses were catheterized for serial measurements of heart rate, arterial pressure, blood gases, metabolites, and electrolytes. RESULTS: Repeated maternal betamethasone injections reduced birth weight (P = .03) without fetal hypoxemia or hypoglycemia. Circulating fetal calcium and lactate concentrations were reduced (P = .002 and P = .014, respectively) by repeated maternal betamethasone only. Fetal hematocrit tended to be lower after fetal (P = .3) and maternal (P = .07) betamethasone. CONCLUSION: Growth restriction caused by repeated maternal hetamethasone treatments is not due to overt chronic placental insufficiency but may be caused by alterations in hormonal mediators of fetal growth or impairment of placental transport of specific nutrients. (J Soc Gynecol Investig 2003; 10:474-9) Copyright (C) 2003 by the Society for Gynecologic Investigation.