In this study we report on the effect of urokinase fragments on the proliferation of cells of the human epidermal cell line, CCL 20.2, which expresses high-affinity receptors for urokinase and the growth of which is stimulated by intact active 54-kDa urokinase. The 33-kDa fragment containing only the active-site domain, does not bind to the receptors and does not stimulate cell proliferation, while the 17-kDa fragment, containing only the kringle and the growth-factor domains binds to the receptor but does not stimulate growth of the human epidermal cell line. Growth promotion of this tumor cell line by urokinase is therefore restricted to the complete intact and active urokinase molecule.