Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected s.c. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl at 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy at 27 d. Tracheas were cannulated and a volume-pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min at each pressure (P) increment of 5 cm H2O. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine-exposed lungs differed from controls as follows:I) wet lung weights were lower (0.79versus0.89 g,p< 0.02);2) opening pressure was lower (P25versusP35);3) volume (ml/kg) was higher in treated animals at each pressure step (p< 0.05);4) end-deflation volume at P0 was higher (30.4versus0.8 mL/kg,p< 0.001); and5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septal walls than controls. We conclude that fetal exposure to cocaine results in increased lung distensibility and stability, induction of low surface tension, and morphologic transformations, each of which is consistent with accelerated lung maturation. The cortisol surge suggests a steroid-mediated mechanism for this effect.