This study describes the clinical signs, hematological changes, and pathologic features of experimental equine endotoxemia. Each of 16 adult ponies was given 40 (mu)g/kg of Escherichia coli lipopolysaccharide intravenously. Five ponies died within 10 hours after treatment began. The other 11 ponies were killed, two each at 8, 16, 32, 36, and 40 hours post infusion (PI) and one at 26 hours PI;Clinical signs progressed through three distinct phases. The first phase was characterized by cyanotic mucous membranes, sweating, and lethargy that developed into ataxia followed by prostration. These signs were first observed within 15 minutes of beginning infusion and persisted for a maximum of 10 hours PI. Five ponies became comatose and died during this first period. The remaining 11 ponies progressed to a second stage characterized by being more alert, drinking water and urinating, and near normal mucous membrane color but with intermittent diarrhea and quadrapedal laminitis. The third stage was a slow progressive development of circulatory insufficiency with slowly developing cyanosis, dyspnea, and prostration in ponies 26 to 30 hours PI;Hematologic changes began with hemoconcentration, thrombocytopenia, hyperproteinemia, and leukopenia at 15 minutes PI. Leukocytosis was seen 7 hours PI because of a neutrophilia with many immature cells. A consumptive coagulopathy developed with gradually increasing activated clotting, prothrombin, and activated partial thromboplastin times;Cecal and colonic lesions were present in all ponies. The cecum and ventral colon were distended with fluid and gas. Large intestinal lesions included hyperemia, edema of submucosa and laminae propria, hemorrhage, ulceration of mucosa, and disruption of mucosal epithelial tight junctions. Lesions in the large intestine were caused by vascular damage. Vascular lesions were characterized by loss of endothelial integrity, suffusion of vascular fluid, and dissolution of basal laminae. Lesions were most severe after 32 hours PI. Bilateral adrenal cortical congestion, hemorrhage, edema, and necrosis were present in all ponies and lesions were more severe at progressively later examinations;Experimental equine endotoxemia produced clinical illness and lesions similar to those of natural cases of acute colic-shock syndromes in the horse.