A double-blind, randomized study comparing the antepartum use of betamethasone (12 mg), methylprednisolone (125 mg), and hydrocortisone (250 mg) was performed to evaluate effect on neonatal respiratory distress syndrome and perinatal infection. Of 144 mothers and 149 infants entered, 92 mothers and 97 infants were available for analysis. The betamethasone-treated group had a significantly reduced incidence of severe respiratory distress syndrome (4%) compared with the control group (26%; p = 0.038); this effect was confined to patients who received at least two doses. No similar effect was found in the methylprednisolone or hydrocortisone groups. Neonatal infection and neonatal mortality rate were not affected by glucocorticoid use. Maternal infection was significantly increased in hydrocortisone-treated patients who were delivered vaginally compared with control patients (all patients: 50% versus 9.5%, p less than 0.05; with ruptured membranes: 63% versus 15%, p = 0.04). No similar increase in maternal infection was found with betamethasone or methylprednisolone use.