DBA/2 mice are highly susceptible while BALB/c mice are resistant to the induction of tolerance with ultracentrifuged BGG. As measured by the clearance of a test dose of 125I-BGG, 2 mg ultracentrifuged BGG is sufficient to induce complete tolerance in DBA/2 mice, while BALB/c mice exhibit a clearance rate similar to immune controls. BALB/c mice pretreated with carrageenan (a macrophage toxic agent) lose their resistance to tolerance induction with 2 mg ultracentrifuged BGG, while treatment with cobra venom factor does not alter their resistance to tolerance induction. Stimulation of the reticuloendothelial system with BCG produces a reduction in the susceptibility to tolerance of DBA/2 mice. This effect is transitory, with the maximum effect 3 weeks after BCG infection. Biologic filtration of BGG through BALB/c mice results in a preparation which is highly tolerogenic for recipient mice and this ability to filter the immunogenic portion of BGG is radioresistant. The results provide evidence for the concept that the differential susceptibility to the induction of tolerance is related to a macrophage function in the inductive phase of immunity.