Cockleburs (Xanthium spp.) are herbaceous annuals with worldwide distribution. Toxicoses are usually associated with the consumption of the seedlings in the cotyledon stage, which contain a high concentration of the toxic principle, carboxyatractyloside. The seeds are also known to contain the toxin, but it has long been assumed that the spiny capsule would deter their consumption. Six of 70 yearling calves died while being fed round bale hay composed predominantly of foxtail and mature cocklebur plants with burs. Clinical signs ranged from acute death to hyperexcitability, blindness, tense musculature, and spastic gaits with heads held high and ears erect. Some symptomatic calves would stumble, fall to lateral recumbency, convulse, and later recover. Overall, the herd was very uneasy. Prominent gross lesions were ascites and a firm, pale liver with a mottled hemorrhagic pattern on cut surface. The rumen contained numerous intact burs and well-ruminated grass. Histological examination of the liver revealed marked centrolobular degeneration and necrosis with associated hemorrhage and congestion. Brain lesions were present. Plant and tissue samples were analyzed for carboxyatractyloside with various results. Samples of rumen contents, urine, and burs contained 100-200 ppm, 0.1-0.05 ppm, and 0.1 ppm, respectively. Based on the history, clinical signs, pathological lesions, and chemical analyses, cocklebur toxicosis associated with consumption of mature Xanthium strumarium in hay was confirmed.