The disappearance of the characteristic supranuclear vacuole and extensive apical canalicular system from enterocytes of the ileal villi occurs during the third postnatal week in rats. This phenomenon is associated with loss of permeability of these cells to macromolecules and is therefore termed closure. The present study was designed to analyze the influence of neonatal guanethidine (GTN)-induced sympathectomy on the morphology of the pre- and postclosure ileum of the rat. Light and electron microscopy of control and GTN-sympathectomized rats demonstrated the retention of immature, vacuolated cells on ileal villi as late as 23 days postnatally in GTN-treated rats. Villi from control rats contained only adultlike nonpermeable cells. Electron microscopy further demonstrated no structural differences in the apical canalicular system or storage vacuoles of the delayed cells in GTN rats when compared to the ileal epithelium from preclosure time periods (7 and 15 days) in both GTN-sympathectomized and control rats. Goblet cells were counted on Periodic-Acid-Schiff-stained sections of ileum from 7, 15, and 23-day GTN and control rats. The percentage of goblet cells in the total epithelial cell population of the villus was significantly higher in control versus GTN rats at all time periods. The percentage of goblet cells increased in both groups from day 7 to 15. However, closure in the control group (approximately day 18) was coincident with a steep increase in the percentage of ileal goblet cells which was not evident in the goblet-cell population of the GTN villus. This pattern of change in control versus GTN goblet-cell production was correlated with a similar pattern of variation in the number of crypt cell mitoses between the two groups over the same time period.