Strains of Lactococcus lactis are present in various natural environment or fermented products, and have been used as starters. In this review, we firstly discuss the immunomodulatory effects of Lactococcus strains from the perspective of their strain-specificity. Forty-six different Lactococcus strains were investigated for their ability to induce cytokine production in the murine macrophage-like cell line, J774.1. Strain-specificity and heat stability related to the ability of Lactococcus cells to induce interleukin (IL)-6, IL-12 and TNF-α, and induce cell necrosis or apoptosis were discussed. Secondly, to examine the immunomodulatory effects of Lactococcus cells in vivo, the effects of oral administration of four strains were investigated for their ability to regulate IgE production in ovalbumin-sensitized mice. Among the four strains, only L. lactis strain C59 showed a significant reduction in the total IgE antibody levels in serum. This suppressive effect on IgE antibody production was lost when strain C59 was heat-killed. Experiments using splenocytes of mice administered with live strain C59 indicated that the suppression of IgE antibody production by live strain C59 was due to the suppression of IL-4 production. The strain-specific immunomodulatory effects of Lactococcus strains are discussed.