In rodents, shortly after birth a lack of increase in pancreatic weight and in islet mass have been reported during a time of overall body weight increase. To understand this regulation of the neonatal growth of the beta cell mass, we studied Sprague Dawley rats at 2, 9, 13, 17, 20, 24, and 31 days of age for beta cell replication, beta cell mass, and cell size and for the presence of cell apoptosis. beta cell mass was stable from 2-20 days (range: 0.91 +/- 0.2 to 1.33 +/- 0.23 mg) and increased thereafter. beta cell replication progressively decreased. Condensed apoptotic nuclei were identified and counted on paraffin sections using the fluorescent dye propidium iodide. Apoptotic beta cell nuclei were found at a basal rate (1.54 +/- 0.22%) at 2, 9, and again after 20 days of age. However, at 13 and 17 days, the incidence of apoptosis was significantly increased (3.64 +/- 0.45%). The decreased replication and the increased incidence of apoptosis in the beta cells strongly suggest a wave of neogenesis of beta cells to maintain the constant beta cell mass. These data show that the endocrine pancreas undergoes significant modification during neonatal life and that apoptosis is an important mechanism in this remodeling of the beta cell mass. Whether a selective deletion of some population of beta cells occurs is unclear, but a dysregulation of this remodeling process could have important effects on the pancreatic beta cell mass.