Technical Abstract: Rayless goldenrod (Isocoma pluriflora) sporadically poisons livestock in the southwestern United States. Similarities with white snakeroot (Eupatorium rugosum) poisoning and nearly identical chemical analyses lead early research to conclude trematol, a mixture of benzofuran ketones is the rayless goldenrod toxin. To date these ketone toxins are not been fully characterized nor are the pathogenesis and sequelae of poisoning completely understood. The objective of this study was to characterize and describe the histologic changes of rayless goldenrod toxicity in goats. Fifteen goats were gavaged with rayless goldenrod to obtain benzofuran ketone doses of 0, 10, 20, 40, and 60 mg/ kg/day. After 7 treatment days, the goats were euthanized, necropsied and tissues were processed for microscopic studies. After 5 or 6 days of treatment, the 40 and 60 mg/kg goats were reluctant to move, stood with an erect stance and became exercise intolerant. They had increased resting heart rate, prolonged recovery following exercise, and increased serum AST, ALT, LDH, and CK activities. All treated animals developed skeletal myopathy with dose related distribution and severity. The 20 mg/kg and higher goats also developed myocardial degeneration and necrosis. Although skeletal myonecrosis was patchy and widely distributed, the quadraceps femoris was consistently damaged, even in low dose animals. Myocardial lesions were most severe in the papillary muscles of 60 mg/kg animals. This indicates that goats are highly susceptible to rayless goldenrod poisoning and the characteristic lesion of poisoning is skeletal and cardiac myonecrosis.