We studied the change in ion transport function by measuring the basal transepithelial potential difference (PD) across the ciliated epithelium of the nose in 85 term neonates during the first 72 hours of life. Differences in PD associated with the mode of delivery or the presence of respiratory disease and differences in the PD response to the superfusion of amiloride (10(-5) mol/L) were assessed. We also studied term neonates with transient tachypnea of the newborn (TTN) and acute respiratory insufficiency. Basal PDs during the first 24 hours of life were higher in neonates delivered by cesarean section without prior labor (-29.7 +/- 2.5 mV) and in those with TTN (-38.5 +/- 6.0 mV) than in neonates born during normal spontaneous vaginal delivery (-23.0 +/- 2.9 mV) or cesarean section with prior labor (-23.7 +/- 0.7 mV) or in those with respiratory insufficiency (-22.4 +/- 2.3 mV). The percentage inhibition of PD by amiloride superfusion (less than 24 hours) was significantly lower in infants with TTN (30.9 +/- 4.9%) and after cesarean section without prior labor (31.8 +/- 2.2%) than in other groups (37.6 +/- 1.6%). By 48 hours, nasal PDs after cesarean section without prior labor and in neonates with TTN had declined; and by 72 hours, values were similar to those in other groups; respiratory rate paralleled the decline in PD. The respiratory rate of neonates with respiratory insufficiency remained high and paralleled the persistence of respiratory distress. Amiloride sensitivity was similar for all groups by 72 hours. These findings indicate (1) that PDs vary with the mode of delivery and support a role for labor in the normal transition of respiratory epithelial ion transport and (2) that TTN is associated with abnormal epithelial ion transport.