Effects of orally administered lactoferrin (LF) on the cellular and humoral immune responses in mice subjected to immobilization stress (IS) were investigated. Here, we demonstrate that long-term IS induced significant suppression of cellular and humoral immune responses in CBA mice. The suppression was attenuated by LF given to mice in drinking water as determined by the number of antibody-forming cells (AFC) in the spleen and the magnitude of delayed type of hypersensitivity (DTH). On the other hand, LF lowered the elevated DTH response in mice exposed to short-term IS (5 h only) on the day of elicitation of the DTH reaction. We also showed that LF up-regulated spontaneous transforming growth factor beta (TGF-b) production in the cultures of mesenteric lymph node cells derived from short-term stressed mice. This is the first report on the regulatory effect of LF on the immune response modified by the psychic stress and is consistent with other reports on antinociceptive and analgesic actions of LF in experimental animals.