The transient ventilatory responses to hypercapnia were studied in nine healthy preterm infants. We administered 4% CO2 in air for at least 7 min during quiet sleep and measured frequency (f), inspiratory time (TI), expiratory time (TE), tidal volume (VT), and minute ventilation (V̇I). Frequency increased over the first 2 min of CO2 inhalation (P < 0.05) and then decreased to control values (P < 0.05). This response was secondary to changes in TE, which decreased over the first 2 min (P < 0.05) and then returned to control values, whereas TI did not change. The late increase in TE was associated with an increased percent of breaths exhibiting retardation of expiratory flow (braking) (P < 0.05). These breaths had longer TE than the breaths without braking (P < 0.05). Exponential curves made to fit the increases in V̇I and VT revealed that only 67% of the infants reached 90% of steady state for both V̇I and VT over the 7-min study period. The time to 90% of steady state was always shorter for V̇I than VT (P < 0.05) due to the transient changes in f. The results indicate that the transient changes of f in response to hypercapnia are secondary to changes in TE, which appear unique to human infants. We speculate that the expiratory braking that develops during the course of CO2 inhalation increases lung volume, resulting in prolongation of TE via mechanoreceptor-mediated reflexes.