Two hundred ninety-seven patients from the placebo group of the National Institutes of Health Collaborative Study on Antenatal Steroid Therapy for prevention of respiratory distress syndrome were selected for analysis to investigate a possible association between premature rupture of the membranes, tocolytic therapy, and respiratory distress syndrome. Both premature rupture of the membranes and tocolytic therapy with isoxsuprine were individually associated with a lowered incidence of respiratory distress syndrome. However, when present together, their protective effect was not additive and resulted in a higher incidence of respiratory distress syndrome. It is suggested that the use of tocolytic therapy with beta-adrenergic agents be restricted to patients with intact membranes.