The renal epithelium appears to be an important target tissue for retinoic acid and epidermal growth factor (EGF). We report here that retinoic acid enhances the proliferative effect of EGF on glomerular epithelial cells (GEC) in vitro and also increases EGF binding to GEC. When GEC were exposed to EGF ( ≥ 1 ng/ml), cellular DNA synthesis was markedly increased. Moreover, the stimulating effect of EGF was synergistically increased by retinoic acid at 5 μg/ml. 125I-EGF binding to cultured GEC was increased approximately 3-fold after addition of retinoic acid to cultures for 48 h. Analysis of 125I-EGF binding revealed 8.1 × 10 receptors per control (untreated) cell, while retinoic acid-treated cells demonstrated an increase to 14.3 × 104 receptors per cell with no detectable change in receptor affinity. These findings suggest that interactions between retinoic acid and EGF may play an important role in the regulation of GEC gr