The neural control of micturition undergoes marked changes during the early postnatal development. During the first few postnatal weeks, the spinal micturition reflex is gradually replaced by a spinobulbospinal reflex pathway that is responsible for micturition in adult animals. Upregulation of brainstem regulation of spinal micturition pathways may contribute to development of mature voiding patterns. We examined the expression of corticotropin-releasing factor (CRF), present in descending projections from Barrington's nucleus to the sacral parasympathetic nucleus (SPN), in postnatal (P0-P36) and adult Wistar rats (P60-90). CRF-immunoreactivity (IR) was present predominantly in the SPN region, although some staining was also observed in the dorsal horn and dorsal commissure in L5-S1 spinal segments. CRF-IR in spinal cord regions was age dependent (R2=0.87-0.98). The majority of the CRF-IR in the lumbosacral spinal cord was eliminated by complete spinalization (2-3 weeks). Double-label immunohistochemistry was combined with quantitative confocal laser scanning microscopy to quantify the number and percentage of colocalization between CRF-immunoreactive varicosities and preganglionic somas or proximal neurites in the SPN in postnatal and adult rats. Results demonstrate an age-dependent upregulation of CRF-IR in the SPN region and specifically in association with preganglionic parasympathetic neurons identified with neuronal nitric oxide synthase (nNOS)-IR. CRF-immunoreactive varicosities on or within a 1 microm perimeter of nNOS-immunoreactive somas or proximal neurites also increased with postnatal age. The upregulation of CRF-IR in bulbospinal projections to the SPN may contribute to mature voiding reflexes.