Biozzi's high and low lines of antibody producers have been applied to an analysis of murine in vivo responses to Brucella. High responders (H/Ab) are better producers of anti-Brucella antibodies and of Brucella induced interferon than low responders (L/Ab). There is no interstrain difference between H/Ab and L/Ab mice as regards to cutaneous hypersensitivity reactions to melitin. Non-immunized L/Ab mice are more resistant to infection with live Brucella than H/Ab. Immunization with formalin killed Brucella leads to a specific protection of both H/Ab and L/Ab mice but magnifies their inter-strain differences: L/Ab are much better protected by preimmunization than H/Ab. The difference between H/Ab and L/Ab mice is not related to an earlier clearance of intravenously inoculated bacteria from the blood stream but to later events affecting the balance between multiplication and digestion of the injected bacteria in the spleen. The lower resistance of H/Ab mice is not due to negative, facilitating-like, activities of immune antibodies: on the contrary, these are shown to have protective properties. These results are discussed in terms of their contribution to present knowledge on Biozzi's mice and their macrophagic functions, on the relations between interferon synthesis and the immune system, and on the mechanism of natural and post-vaccinal protection toward Brucella.