We have previously shown that the strength of the Hering-Breuer inflation reflex (HBIR) diminishes between 2 and 12 mo of age in full-term babies. The purpose of this study was to determine whether the onset of this decline had commenced by 3 to 4 mo of age in healthy full-term infants and whether preterm delivery influences the pattern of maturation. Serial measurements of HBIR activity using the end-inspiratory occlusion technique were made in 25 preterm and 27 full-term infants at matched postnatal and postconceptional ages during the first 6 mo of life. Although similar levels of reflex activity were observed at birth (mean +/- SD of 101.2% +/- 42.4% in preterm, and 101.0% +/- 33.9% in full-term infants), by 40 wk postconceptional age (PCA) (i.e., term equivalent) HBIR activity (mean +/- SD) had increased to 121.7% +/- 51.2% in preterm infants, which was significantly greater than that in full-term infants of similar PCA (95% CI of difference: 0.2; 41.2%). By 15 wk postnatal age (PNA), HBIR activity had decreased to 68.8% +/- 26.6% in full-term infants, but remained significantly higher in those delivered prematurely (87.8% +/- 32.7%). However, when measurements were repeated at approximately 4 mo after the expected rather than actual date of delivery, these differences were no longer evident (95% CI difference preterm-full-term: -21.2; 3.8%). This study suggests that important transitions in respiratory control mechanisms occur between 8 and 15 wk PNA in full-term infants and that these changes are delayed in preterm infants.