Evidence is growing that autoimmune reactivity results from a combination of endogenous (e.g. MHC type) and environmental factors. Our experimental study focuses on the induction of autoimmune reactivity by microbial factors. Splenic formalion and serum levels of antierythrocyte antibodies and circulating immune complexes were taken as parameters. It was found that experimental infection of mice withEscherichia caliandSalmonella typhimuriumwas accompanied by clear signs of autoimmune reactivity, smooth bacteria being almost ten times as potent as rough mutant strains. An attempt was made to correlate the data obtained with live bacteria to their corresponding endotoxins. It was concluded that the induction of more prominent autoimmune reactivity by smooth bacteria must be ascribed to a longer survival timein vivo.Our data support the view that bacterium-derived factors are involved in the etiology (and possibly also the course) of autoimmune diseases.