SUMMARY Human peripheral blood lymphocytes were treated with three enzymes and their subsequent ability to form spontaneous rosettes with sheep red blood cells (SRBC) was studied. Prior treatment of the lymphocytes with papain greatly increased the proportion of rosette-forming cells (RFC) per 103 lymphocytes. Trypsin and phospholipase A treatment decreased this number. Lymphocytes recovered spontaneously after removal of phospholipase A, but not after removal of trypsin or papain under the conditions used. Soluble material from phospholipase A treatment of lymphocytes inhibited rosette formation. The possible mechanism of action for each enzyme is discussed.