Three groups of Sprague-Dawley CD rats (males and females) were initially administered p.o. with ebrotidine, a novel H 2 -receptor antagonist, mixed with the diet, at 50, 200, and 500 mg/kg/d, respectively. Two concurrent control groups of animals were used. After 13 months, initial 200 mg/kg was lowered to 150 mg/kg, and a new group was administered with 300 mg/kg, due to the body weight reduction observed in the top dose group. After 24 months, survivors were killed and necropsied, and a histopathological study was performed. The frequencies of the different tumour types that were found were not raised due to the treatment. Lower frequencies of some types of pituitary and mammary gland tumours, in the groups treated with the higher doses, were the only statistically significant changes. Among the non-neoplastic effects, a lower body weight increment and food consumption (500 and 300 mg/kg, both sexes), lower survival (500 mg/kg, males), presence of lipoid pneumonia (500 mg/kg, only in males, and 300 mg/kg, both sexes), and lithiasis in urinary system (500 mg/kg) were observed. No changes in gastric mucosa (the main target organ) were attributable to ebrotidine. Regarding the non-neoplastic effects, 150 mg/kg was the no observed adverse effect level. According to the previous results of the carcinogenicity study in mice, conjointly with those of the study in rats reported here, there is no evidence of carcinogenic risk either in males or in females in these species.