BACKGROUND Lactoferrin belongs to the immunoregulatory milk proteins involved in iron metabolism as well in providing innate immunity to newborns. The protein has been the subject of numerous clinical studies. OBJECTIVE The aim of this investigation was to evaluate the effects of bovine lactoferrins (bLF), differing in source and iron content, on spontaneous proliferation of human peripheral blood mononuclear cells (PBMC) and cytokine production by human whole blood cultures. METHODS The following bLF preparations were used: partially iron saturated or devoid of iron bLF from milk and bLF from colostrum. The study was conducted on 12 healthy volunteers (men, 20-24 years old). The effects of bLFs on the proliferation of PBMC in four-day cultures was studied at 50-0.6 µg/mL concentration range and the rate of proliferation was determined using the MTT colorimetric method. TNF α and IL-6 levels, induced by the bLFs in 24 h whole blood cultures, were measured by ELISA. RESULTS The lactoferrins stimulated autologous proliferation of human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner, with a comparable efficacy. This stimulation occurred both in the constant presence of bLFs in the cultures and also upon preincubation of PBMC with bLFs with subsequent exhaustive wash of cells. Only bLF from colostrum induced production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in cultures of whole blood cells. This phenomenon took place predominantly at concentration of 50 µg/mL. CONCLUSIONS The results showed potent stimulation of the proliferative response of PBMC by bovine lactoferrin, associated with the induction of proinflammatory cytokines only in the case of colostral bLF. This observation may be of importance when high doses of bLF are used in therapy and by designing diet supplementation with this protein.