Ponies given dried red maple (Acer rubrum L.) leaves at a dose of 3.0 gm/kg body weight became ill and died one to five days after administration of the leaves. Two clinical patterns of disease were seen. Ponies given dried leaves collected after September 15 died by 18 hours, while ponies given dried leaves collected before September 15 became ill with a hemolytic syndrome and died by three to five days. Freshly harvested leaves administered immediately after collection did not produce disease in ponies, but when dried, they became toxic and remained so for at least 30 days. Overnight freezing did not alter the toxicity of the leaves. Leaves were toxic when administered at doses of 1.5 gm/kg of body weight. The clinical signs of ponies with the hemolytic syndrome included polypnea, tachycardia, icterus, cyanosis, scleral petechiation, and brownish discoloration of the urine and blood. Blood changes of ponies with the hemolytic syndrome included anemia, hemoglobinemia, Heinz bodies, depletion of erythrocyte reduced glutathione, increased erythrocyte fragility, and increased serum levels of aspartate amino transferase, sorbitol dehydrogenase, plasma protein, and bilirubin. Lesions of ponies that died from the hemolytic syndrome included icterus, centrilobular hepatic degeneration, hemoglobinemic nephrosis, and erythrophagocytosis by splenic, adrenal, and hepatic phagocytes. Only brownish discoloration of the blood and mild centrilobular hepatic degeneration were observed in the four ponies that died peracutely.