A normal human plasma low density lipoprotein subfraction (LDL-In), recovered within the intermediate density lipoprotein subclass of density range 1.006 to 1.019 g/ml, has previously been demonstrated to bind to a specific cell surface receptor independent of the LDL receptor and to regulate inductive events in the triggering of lymphocytes. The constituents of LDL-In that are responsible for the biologic activity and receptor-binding specificity were examined with respect to the role of sterols and other neutral lipids. Partial delipidization of LDL-In with heptane in the presence of starch permitted selective extraction of greater than 98% of the neutral lipids from the native lipoprotein particle. These partially delipidated polar lipid:protein particles were compared with native LDL-In with respect to charge, apoprotein content, suppressive activity for lymphocytes, and specific binding to the lymphocyte LDL-In receptor. The cholesterol- and glyceride-depleted LDL-In retained all characteristics of the native lipoprotein. These observations indicate that the interaction of LDL-In particles with the lymphocyte and the suppression of lymphocyte function are independent of the neutral lipid content of this bioregulatory lipoprotein, and that mechanisms other than cholesterol loading of the cell or sterol exchange with the plasma membrane must be operative.