Thirteen-week oral repeated dose toxicity of ecabapide, a gastroprokinetic drug, was investigated in dogs at dosage levels of 50, 175 or 600 mg/kg, and in rats at dosage levels of 25, 100, 400 or 1600 mg/kg. In dogs, vomiting, aqueous salivation, body weight gain inhibition, and hemolytic anemia, together with an increase in Heinz body formation, were observed at 175 and/or 600 mg/kg. Histological examination revealed enhanced hemosiderin deposition in the liver and spleen, retention of erythrocytes in the splenic sinus and enhanced erythropoiesis in bone marrow at 175 and/or 600 mg/kg. In the rat study, although increases in serum total protein, albumin and calcium, as well as increased liver and kidney weights, were observed at 400 and/or 1600 mg/kg, no obvious morphological changes were seen. The hemolytic anemia and an increased Heinz body formation were not observed in rats, indicating a species difference. On the basis of these results, the non-toxic dose of ecabapide was considered to be 50 mg/kg in dogs and 100 mg/kg in rats.