We have investigated protease-inhibitory activity against cathepsin L of human and murine Ha-ras oncogene products (p21s) produced by Escherichia coli. The inhibitory activity of full-length p21s was much weaker than that of truncated p21s, however, the inhibitory activity was potentiated after denaturation with 8 M urea and 2 M NaCl followed by renaturation. These suggest that p21 can be folded into multiple three-dimensional conformations which have different protease-inhibitory activities.