This study was undertaken to correlate changes in insulin, IGF-1, and IGF-2 receptors in enterocytes both during the phase of active hyperplasia (protocol 1) and the phase of initiation of hyperplasia (protocol 2) induced by 60% proximal jejunoileal resection in rats. Hormone binding to purified receptor preparations, indirect immunofluorescence analysis by flow cytometry, and immunohistochemistry were used to identify receptor changes. Insulin and IGF-2 receptor binding were increased in the intestine two days after surgery and prior to increased cell mass. The number of cells expressing insulin and IGF-1 receptors increased two- and three-fold between 12 and 36 hr after resection, whereas IGF-2 receptors were maintained throughout the 48-hr period. A significant increase in immunoreactive IGF-2 receptors in both the villus and crypt regions of the jejunum and ileum was observed 12 hr after resection, and this increase was maintained in the crypt region of the jejunum through 48 hr. Therefore, insulin and IGF-2 receptors appear to be important in the initiation of cellular hyperplasia following resection.