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The effect of rifampicin on the immune response to sheep red blood cells and the lipopolysaccharide antigen of Escherichia coli in mice and to cholera vaccine in human volunteers was studied. No evidence of an immunosuppressive effect of the drug was found in humans given doses not exceeding those clinically recommended. Primary response was depressed in mice when a large dose of rifampicin was given ip soon after the administration of the antigen. The phagocytic activity of the peritoneal macrophages from mice given rifampicin ip was profoundly curtailed. The correlation between depression of the immune response and reduction of phagocytic activity strongly suggests that the main target of the drug is the phagocytosing cell. [ABSTRACT FROM PUBLISHER]