The hamster cheek pouch has generally been used in oral mucosal irritation test. However, whether the hamster cheek pouch is suited for this test is questionable, because it differs from the oral mucosa histologically. Therefore, we tried to search for a more suitable mucosa for irritation tests in place of the hamster cheek pouch, and found that the rabbit sublingual mucosa was quite ideal for this purpose. That is, the rabbit sublingual mucosa showed a higher sensitivity than the hamster cheek pouch to irritants such as acetic acid and sodium lauryl sulfate. And it showed a similar pattern of injury for each irritant. These results indicated that the rabbit sublingual mucosa was ideal for irritation tests. We also devised a new apparatus by which the tested drug is kept in uniformly close contact with the mucosa for prolonged periods of time. By using our new apparatus, we examined a relationship between the duration of drug application and the intensity of the resulting injury, and a relationship between the concentration of irritants and the intensity of the resulting injury. We determined the duration of application, the appropriate observation time and criteria of the test condition based on our findings that the intensity of injury was dependent on the duration of application or the concentration of irritants, and that the time when the injury reached its peak was the same regardless of the concentration of irritants. The results of our study suggest that our new method would be a highly sensitive technique for the evaluation of the irritancy of drugs on the oral mucosa.