Various experiments indicate that normal growth and differentiation of murine epithelia in vivo are dependent on dermal influences, and the growth-enhancing effects of various connective tissue elements have also been demonstrated in vitro. Such effects were examined by the in vitro growth of murine epidermis on various substrata (collagen, lens capsule) at the air/medium interface with various connective tissue elements or cells apposed to the undersurface of the supporting matrix. Patterns of epithelial growth, morphology and differentiation were examined by histology, electron microscopy, gel electrophoresis and antibody staining. Growth and differentiation varied with differing substrata but good patterns of growth and morphology, and appropriate expression of cytoplasmic and cell surface differentiation markers, were found only in specimens grown in association with dermal elements. It is concluded that diffusible factors of dermal origin facilitate epithelial growth and differentiation.