Antiserum raised to a rough mutant Escherichia coli, termed J5 (anti-J5 RS), protected against lethal gram-negative bacterial sepsis in a guinea pig model when animals were pretreated with both antiserum and heparin. This same model was used to examine and compare the effects of pretreatment with anti-J5 RS, normal rabbit serum (NRS), or saline, each +/- heparin on physiologic and metabolic parameters during a septic insult. Results demonstrated that leukopenia and thrombocytopenia occurred to a similar degree in all pretreatment groups; no significant leuko- or thrombostasis was noted on examination of histologic specimens; complement activation was maximal in those animals receiving anti-J5 RS alone without heparin; the most abnormal amino acid profile was present in the NRS + heparin group; and only the anti-J5 RS + heparin group did not develop glomerular lesions indicative of disseminated intravascular coagulation. A complement-mediated cell aggregation-type injury does not appear to occur in this model. It is hypothesized that both excessive complement and coagulation system activation occur after bacterial challenge when antibody directed against the bacteria is present (anti-J5 RS) leading to antigen-antibody complex formation and complement and coagulation cascade activation. Heparin may block either or both these cascade systems allowing enhanced, antibody-mediated opsonization and clearance of blood-borne bacteria, thus preventing end-organ alterations and organ failure during sepsis when combined with anti-J5 RS.