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The net charge on the cell wall of Micrococcus lysodeikticus has been determined, using cellular electrophoresis measurements, to have a value of -1.5 2 0.05 FC/cm' from pH 4 to pH 9. Measurements of the lytic activity of lysozyrne'toward M . lysodeikticus as a function pH and ionic strength of the supporting electrolyte, have been analyzed in terms of the theories of polyionic solutions and electrical double layers. The electrostatic field near the cell wall surface is shown to influence the enzyme activity by causing local shifts in pH, which are ionic strength dependent. It is also shown that, at high ionic strengths, the activity is aided by electrostatic forces of attraction between lysozyme and the cell wall, whereas at low ionic strengths a negative charge on lysozyme (of magnitude around one electronic charge) produces a repulsive electrostatic force which hinders the activity. The negative charge is proposed to be ionized Asp 52 at the enzyme-active site.