We examined the respiratory response to moderate hypercapnia in rat pups during the first 10 days after birth and also studied immediate early gene expression to investigate whether areas described as chemosensitive in the adult rat are activated also in the early postnatal period. Breathing frequency increased in 1- and 3-day-old pups, but decreased in older animals in response to hypercapnia. Tidal volume and ventilation increased significantly in all age groups but relatively more in the 10-day-old pups as compared to younger animals. In situ hybridisation for c-fos mRNA revealed increased expression in several of the areas assigned as chemosensitive in the adult, including the caudal nucleus tractus solitarii and the ventral lateral medulla. In contrast, locus coeruleus and the majority of midline raphe neurons did not exhibit increased expression of c-fos mRNA. We conclude that the hypercapnic respiratory response tends to decrease during the first postnatal week, but thereafter increases on day 10 due to increased tidal volumes rather than changes in respiratory timing. We also speculate that differences in activation of chemosensitive brainstem neurons may be part of the maturation of the hypercapnic ventilatory response.