Three groups of dogs were given lipid X (0, 1, or 10 mg/kg) every 8 h for for seven doses, starting simultaneously with the intraperitoneal placement of Escherichia coli-containing fibrin clots. All animals developed bacteremia, hypotension, and a pattern of decreased left ventricular ejection fraction characteristic of septic shock (P = .01). Survival rates and survival times were not significantly different between treatment groups (P > .2). In a similar experiment, higher doses of lipid X resulted in a significantly decreased survival time compared with concurrent controls (P = .04). Animals receiving lipid X did not differ from controls in serial determinations of temperature, hemodynamic measurements, or laboratory parameters (except serum total protein). Although lipid X has antiendotoxin effects, no benefit could be demonstrated in this antibiotic-treated, gram-negative bacillary-infected model of septic shock. These data do not support a therapeutic role for lipid X in the treatment of gram-negative sepsis.