Immunofluorescence studies showed that properdin (P) and factor B bind to C3-C3b receptor bearing human lymphoblastoid cells (Raji, Daudi) and B type human peripheral lymphocytes (HPL). P bound to Raji cells first incubated with normal human serum (NHS). EDTA, but not EGTA, halted the binding of P to cells incubated with NHS. However, fixation of P to Raji cells, after incubation with NHS first reacted with inulin, was independent of Ca++ and -g++ ions. Fixation of P to Raji cells depended on the presence of C3 or C3b and occurred in the absence of factor D and factor B. Binding of P to B type HPL was detectable only after incubation of these cells with NHS first reacted with inulin; under these conditions binding of P to Raji cells was also greatly enhanced. With both Raji cells and HPL, factor B was detectable on cell surfaces only after incubation of these cells with NHS first reacted with activators of the P system. Binding of factor B to cells required the presence of C3b and binding or stabilization of cell bound factor B necessitated the presence of activated P. P and factor B were detectable only on cultured cells having C3-C3b receptors. However, incubation of NHS with all lymphoblastoid cell lines studied resulted in activation of P and cleavage of factor B. Binding of P and factor B to cells may follow one of three sequences; (a) activated P in fluid phase combines with C3, factor D, and factor B, and the whole complex fixes to cellular C3-C3b receptors via its C3 moiety; (b) C3b generated in fluid phase combines with P, C3, factor D, and factor B and binds to C3-C3b receptors; or (c) C3 or C3b first binds onto the C3-C3b receptors and thereafter interacts with P, factor D, And factor B. Binding of components of the P system to cells or other particles may relate to such biological phenomena as lysis, phagocytosis, proliferation, attraction of other cell types, and alteration of responsiveness to external stimuli.