The effects of residual β-cell mass and glycemia on regeneration of endocrine pancreas after 90% pancreatectomy were investigated. Streptozotocin or buffer alone was injected into 4-wk-old male Lewis rats ( day 0). On day 7, varying numbers of syngeneic islets were transplanted under the kidney capsule to achieve varying degrees of glucose normalization. On day 14, a 90% pancreatectomy or sham pancreatectomy was performed. On day 19, rats were killed and the pancreas was fixed for quantitative morphometric determination of β-cell mass. Focal areas of regenerating pancreas were observed in all animals that underwent partial pancreatectomy. The percentage of remnant pancreas classified as foci was unaffected by streptozotocin treatment or by plasma glucose. Moderate to severe hyperglycemia did not promote regeneration of the pancreatic β-cell mass; rather the total endocrine cell mass was inversely related to the plasma glucose level ( r = −0.5, P < 0.01). These data suggest that the precursor population for both endocrine and exocrine tissue is not susceptible to damage by streptozotocin and that local effects of residual β-cell mass are not important to regeneration after a 90% pancreatectomy.