Supplementary surfactant (80 mg in 1 ml) was administered intra-amniotically in proximity of the fetal mouth to 4 preterm fetuses (28 to 32 wks) with immature amniotic fluid indexes and whose delivery was imminent. Administration was preceded by a aminophylline infusion (loading dose of 240 mg and maintenance of 0.8 mg/kg/min) to the mother in order to elicit sustained fetal breathing movements. Following delivery by cesarean section, the absence of signs of respiratory distress in the infants along with a completely uneventful clinical course suggests that the present therapeutic approach has great potential for becoming a reliable option for the antenatal prevention of RDS.