Specific binding of iodine 125-labeled epidermal growth factor was measured in membrane homogenates of third-trimester and term human placentas of male and female fetuses. All placentas (n = 35) generated curvilinear Scatchard plots, and all placentas had similar equilibrium dissociation constants for both high-affinity (210 pmol/L) and low-affinity (830 pmol/L) binding sites. Mean maximum number of available binding sites of term placentas from male fetuses (330 +/- 110 fmol/mg protein; n = 11) was significantly higher (p less than 0.001) than that of female fetuses (170 +/- 80 fmol/mg protein, n = 13). Occupation of epidermal growth factor receptors by endogenous epidermal growth factor could not account for the difference in levels of epidermal growth factor binding. Kendall's rank order correlation test demonstrated a significant positive correlation of the gestational age in weeks with the maximum number of epidermal growth factor receptors in placentas from male fetuses (p less than 0.002; T = 0.527; n = 17) and female fetuses (p less than 0.01; T = 0.404; n = 18). These results indicate that there is a sexual dimorphism in the level of epidermal growth factor receptors in placentas of male and female fetuses during the third trimester and that the level of epidermal growth factor receptors increases during the third trimester for placentas of both male and female fetuses.