Background: Lung type II cell differentiation is predominantly regulated by fibroblast-type II cell communication. We have shown that EGF-R activation influences this process. EGF-R expression in fetal lung fibroblasts may control the timing of fibroblast-type II cell communication.Hypothesis: Hormones and growth factors which influence lung cell differentiation regulate EGF-R activity. Subjects: Sex-specific fetal rat lung fibroblasts at d17, d19, and d21 (term = d22).Intervention: Cells were treated with either a positive [EGF, cortisol, retinoic acid (RA)] or negative [transforming growth-factor-ß1(TGF-ß1), dihydrotestosterone (DHT)] regulator of lung cell differentiation for 5 days. EGF-R binding and Westerr blots for EGF-R protein were performed. Results: RA significantly increased (four- to eight fold) EGF-R binding as compared to controls in both sexes and all three gestations. DHT treatment significantly stimulated binding in female cells(two- to fourfold) on d17 and d19, and also significantly stimulated males(fivefold) at d21. TGF-ß1 significantly stimulated binding in female cells on d21 of gestation (threefold). Western blot analysis in d17 and d19 fibroblasts showed similar increase of EGF-R protein. Conclusion: Factors that regulate the initiation of developmental differentiation regulate EGF-R binding even after cell-cell communication is established Such factors continue to regulate lung developmental differentiation