An early hypotensive phase was induced in rats by different strains of Escherichia coli and cell wall fractions to study the role of the bacterial surface structure, the complement system, histamine, and serotonin in induction of hypotension. E. coli strains with only core glycolipid (E. coli strain J5) or with intact lipopolysaccharide O antigens on their surface induced hypotension and thrombopenia within 5 min after intravenous administration. This response was reduced by prior decomplementation of the rats and by methysergide, a serotonin antagonist. Two K antigen-positive strains induced no hypotension except after removal of K antigen. The isolated lipopolysaccharide fractions and the lipid A subfractions, but not the polysaccharide subfractions, were also able to induce hypotension. Thus the core glycolipid structure, by interactions that involve platelets and the complement system, is mainly responsible for induction of an early hypotensive phase in rats, and K antigens interfere with this response.