OBJECTIVE: We evaluated lung maturation responses to the mixture of betamethasone phosphate (Beta-PO4) + betamethasone acetate (Beta-Ac) in comparison to Beta-PO4 or Beta-Ac in fetal sheep. STUDY DESIGN: Ewes carrying singleton pregnancies at 122 days of gestation were randomized to single doses of 0.5 mg/kg Beta-PO4 + Beta-Ac, 0.25 mg/kg Beta-PO4, 0.5 mg/kg Beta-PO4, or 0.25 mg/kg Beta-Ac given 48 hours before delivery. These treatments were compared with saline placebo and 2 doses of 0.5 mg/kg Beta-PO4 + Beta-Ac that were given 48 and 24 hours before delivery. Fetal lung maturation was evaluated. RESULTS: The 2 doses of the Beta-PO4 + Beta-Ac mixture gave the best lung maturation. Single doses of the Beta-PO4 + Beta-Ac mixture and Beta-Ac alone also induced lung maturation. There were no consistent responses to either dose of Beta-PO4. CONCLUSION: Beta-PO4 alone is ineffective with the dosing schedule used; Beta-Ac can induce lung maturation. However, the best responses result from the mixture of Beta-PO4 + Beta-Ac.