Previously, we reported a critical period [around postnatal day (P) 12-13 in the rat] in respiratory network development when distinct neurochemical, metabolic, and physiological changes occur. Since serotonin 2A (5-HT(2A)) receptors play an important role in respiratory modulation, we hypothesized that they may undergo developmental adjustments during the critical period. Semi-quantitative immunohistochemical analyses were conducted in labeled neurons in a number of brain stem nuclei with or without known respiratory functions from P2 to P21 in rats. Our data indicate that the expressions of 5-HT(2A) receptors in neurons of the pre-Bötzinger complex, the nucleus ambiguus, and the hypoglossal nucleus were maintained within a relatively narrow range between P2 and P21, with a dip at P3-P4 and a significant reduction only at P12. This change was not observed in the nonrespiratory cuneate nucleus. These results suggest that reduced expressions of 5-HT(2A) receptors at P12 contributes to neurochemical imbalance within brain stem respiratory nuclei at that time and may be involved in decreased hypoxic ventilatory response at this critical period of development.