The aim of this study was to investigate the effects of bovine lactoferrin on the proliferative response of human blood lymphocytes induced by PHA and alloantigens in two-way mixed lymphocyte culture at a broad range of BLF concentrations (1.5 - 50 mug/ml). We found that the effects of BLF in both experimental models were differential and depended on an individual reactivity of lymphocytes with respect to mitogen or alloantigen and BLF concentration. Generally, lymphocytes from donors reactive to BLF exhibited higher proliferation indices compared to nonreactive individuals. Low BLF doses were regulatory and higher ones mostly inhibitory. MLR was in most cases inhibited by all doses of BLF, some MLR stimulated and other not affected by BLF. We conclude that basis for the differential action of BLF is its ability to sense the activation status of lymphocytes. The resultant effects of BLF are probably mediated by monocytes and cytokines.