The time course of the transient ventilatory response to a sudden change in inspired gas from room air to 4% CO2 in air was examined in 11 healthy preterm neonates. Changes in minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were determined over 4 to 5 min of CO2 inhalation during both quiet (QS) and active sleep (AS) in each infant. In both states there was a brisk increase of mean VI in response to 4% CO2, while mean VT increased more slowly and mean f only increased transiently at 1 to 2 min. Exponential curve fitting to the change in VI and VT for each infant accounted for 64 +/- 20% of the variance in VI during QS as compared to 30 +/- 18% during AS (p less than 0.003). In only six infants did exponential curves fitted to the changes in VI and VT during QS reach 90% of their steady state values within 4 to 5 min of CO2 exposure. Their time to reach 90% of steady state was always shorter for VI than VT (p less than 0.01). Frequency showed a biphasic response with a transient rise at 1 to 2 min (p less than 0.05) and return to control levels at steady state. These data indicate that not all preterm infants reach a new level of steady state ventilation within 4 to 5 min of 4% CO2 inhalation. Furthermore, many infants exhibit a biphasic response of f over time which causes VI to reach steady state prior to VT.