Granulocyte factor derived from the specific granules of polymorphonuclear neutrophils affects mitogen--and alloantigen--induced proliferation of human lymphocytes "in vitro". A dual pattern of GF effect was noted: inhibition of mitogen induced lymphocyte proliferation in higher concentrations and costimulatory activity in lower concentrations of GF. GF induced the lymphocyte proliferation in combination with phorbol ester (PMA) or anti-CD2 monoclonal antibodies (mAb) with PMA. Other combinations of anti-CD2 and anti-CD3 mAb with GF do not augment the proliferation. The comitogenic activities of GF are associated with IL-2 production and IL-2R expression. Specific binding of labelled GF to stimulated lymphocytes suggests that it may recognize the specific molecule expressed only an activated cells. GF diminishes the zymosan-induced granulocyte stimulation, but GF acts as a stimulator of granulocyte O2 production. GF may recognize common targets on leukocytes. Leukocyte adhesive glycoproteins may be such putative targets.