The proteins in culture filtrate derived from Bacillus Calmette-Guerin (BCG) were examined for protection against infection by Mycobacterium leprae. Immunization with the major secreted proteins, antigen 85 complex (Ag 85) A, B and C, induced effective protective immunity against multiplication of M. leprae in the foot pads of mice. The most effective protection was observed when mice were immunized with Ag 85A. A single immunization with Ag 85 could induce antigen-specific interferon γ (IFNγ) synthesis and more effective protection than live BCG vaccine. This study demonstrates that Ag 85 is an important immunoprotective molecule against leprosy infection.