In rats of the Holtzman strain, susceptible to the development of adjuvant induced arthritis (AIA), oral administration of BCG significantly inhibited the development of the disease. Oral treatment with purified protein derivative (PPD) had no effect. In the resistant Buffalo rats, however, oral administration of BCG and PPD enhanced the lesions. Since oral administration of antigens has been described to induce suppressor cells, our results suggest that the development of AIA is controlled by suppressor mechanisms, which fail to be activated in the susceptible strain, but are stimulated by the oral administration of BCG.