Cultures of dividing skin fibroblasts from normal and sclerodermatous human skin have permitted estimations of soluble collagen concentration, net collagen accumulation, cell-doubling times, and the comparison of morphologic and ultrastructural characteristics. In vitro, the scleroderma fibroblast produces more soluble collagen, synthesizes collagen more rapidly, and fourfold more of its protein synthetic activity is directed to collagen production than in the normal skin fibroblast. Cell-doubling times and morphologic and ultrastructural observations of cells in culture have not provided clues to the nature of the biologic defect in the regulation or activation of collagen synthesis by the scleroderma fibroblast.