Immune serum injected into mice before a footpad challenge of virulent strain Brucella abortus 544 can prevent dissemination of infection to the spleen. Sera from mice infected with Brucella for at least 2 months or from mice vaccinated with a protein-bound cell wall peptidoglycan Brucella fraction completely stopped dissemination. Brucella lipopolysaccharide and polysaccharide cross-reacting Yersinia immune sera reduced dissemination. Both peptidoglycan and lipopolysaccharide immune sera injected simultaneously with an intravenous challenge caused a shift in Brucella from spleen to liver. When immune sera were injected simultaneously with an intravenous challenge, the kinetics of splenic infection showed two effects: an early one, optimally measured at day 7 postchallenge, showed reduced numbers in the spleen due to the shift of Brucella to the liver; a late effect, measured at day 21 postchallenge, showed reduced numbers in spleen and liver with nearly complete clearance by day 49 postchallenge. Brucella lipopolysaccharide and cross-reacting bacterial antisera induced the early effect only, whereas peptidoglycan and infected mouse sera induced both effects. When peptidoglycan immune serum was injected 2 or 7 days after intravenous challenge, the late effect was somewhat reduced. Hence, immune sera to protein and polysaccharide surface antigens can (i) prevent dissemination of systemic infection and (ii) help destroy intercellular bacteria (protein antigen only). These effects may represent a large part of vaccinal immunity.