Abstract The development of natural antibodies to Lactococcus lactis in three inbred strains of mice and the effect of inoculating L. lactis into these mice has been investigated. All animals developed detectable levels of natural (systemic and secretory) anti-lactococcal antibodies. Systemic anti-lactococcal antibodies were principally IgG in young mice. An increase in anti-lactococcal IgM occurred in all older animals. Inoculation of L. lactis strains MG1830 or M1363 by the oral and parenteral routes induced systemic anti-lactococcal antibody responses in a dose-dependent fashion. The relative immunogenicity of individual bacterial proteins varied according to mouse strain and route of inoculation.