This study was aimed at characterizing epidermal growth factor (EGF) receptors during postnatal development of the maturing mouse small intestine at a time when this tissue is in the constant presence of high levels of intraluminal EGF. Binding studies with [125I]EGF on isolated epithelial cells demonstrate the continued presence of EGF receptors along the entire length of the small intestine with minimal binding at birth (3.67 +/- 0.30%/mg protein) and increasing steadily throughout postnatal life to reach adult values (10.39 +/- 0.90%/mg protein) by the 26th day, with maximum binding on the 21st day (13.4 +/- 2.2%/mg protein). This EGF binding pattern is similar for all three segments studied but was more pronounced for duodenum and jejunum, especially from day 14 on when binding capacity is more elevated in the proximal segments than in the ileum. Competition-inhibition curves of [125I]EGF by EGF reveal the presence of two classes of binding sites for which the number of sites and affinity constants are lower at birth than in adults. The continued presence of EGF receptors in mouse small intestine throughout the postnatal period thus provides support for the possible role of EGF as a modulator in the functional development of the maturing gastrointestinal (GI) tract.