Live Mycobacterium lepraemurium (MLM) bacilli, bacilli killed by irradiation or heat, and the water-soluble components of ultrasonicated bacilli (MLMSon) were compared as immunizing and eliciting antigens in C57BL mice which are high-responders to live MLM. The latency period preceding the development of a local granulomatous reaction in normal mice inoculated subcutaneously in the footpad with live MLM was reduced, and the reaction became larger when the dose of bacilli was increased. Immunization with MLMSon induced only weak initial reactivity against an inoculum with live bacilli, but the development of stronger reactivity was accelerated and the magnitude of the local reaction that then developed was increased. MLMSon-immunized mice showed some reactivity also against heat-killed bacilli. Killed bacilli caused the development of a small, late local reaction in normal mice, but no local reactivity was detected upon challenge with live and killed MLM in mice immunized with killed bacilli. However, a local reaction was elicited by MLMSon, which was thus a more potent eliciting antigen than intact bacilli, and MLMSon and whole killed bacilli appeared to induce immune reactivity with overlapping antigen specificities. Subcutaneous inoculation with live bacilli induced reactivity against live MLM but not against MLMSon and not against whole killed MLM, except for a transient early (24 hr) reaction elicited only with a large dose of killed bacilli. The development of a lasting local reaction against killed bacilli was found to be suppressed in mice immunized with live bacilli. Live bacilli and dead MLM antigen appeared to have largely different specificities as inducing as well as eliciting antigens.

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