Toxic doses of C. psittaci 6BC strain produced within 3–6 h after inoculation a rapidly progressive irreversible damage of mouse macrophages in vitro, an early leakage of a lysosomal enzyme, acid phosphatase, as well as a rapid disintegration of neutral red-stained cytoplasmic granules i.e. lysosomes. Pretreatment of the agent with immune serum neutralized the cytotoxic action of the agent and a reversible activation of lysosomes occurred. Pretreatment of the agent with undiluted control serum protected the macrophages from the early "toxic" injury; however, a cytopathic effect (CPE) occurred 48 h after inoculation and was accompanied by a release of lysosomal acid phosphatase. Heat-inactivated Chlamydiae produced an early agglutination of macrophages with leakage of lysosomal acid phosphatase, disintegration of neutral red-stained lysosomes, as well as a progressive irreversible damage of the macrophage. Concentrated, heat-inactivated agent-free, leuco-agglutinating material from 6BC infected L cells produced a similar injury of macrophages and their lysosomes. The findings are related to an earlier report of a rapid destruction of macrophages by C. psittaci in the intact animal (15). The possible mechanisms and factors of the "toxicity" of Rickettsiales are discussed.