The role of intestinal bacteria in converting the naturally occurring glucoside cycasin to its hepatotoxic and carcinogenic aglycone (methylazoxymethanol) has been studied. Germfree rats, in which cycasin is nontoxic, were monocontaminated with several strains of bacteria prior to being given cycasin. Levels of glucosidase activity in the bacteria were determined by the assay of cell free extracts, using cycasin as a substrate. The toxicity of cycasin in rats given the various bacteria and the amounts of unchanged cycasin excreted were consistent with the glucosidase assays. Intestinal microorganisms therefore convert cycasin to the toxic aglycone, and variations in the intestinal flora probably have a role in determining the toxicity of ingested cycasin.