Purified protein derivative from Mycobacterium tuberculosis inhibits contact sensitivity to oxazolone in mice when given intravenously 24 to 72 h before the antigen. Transfer experiments showed that various types of suppressor cells occurred in the lymph nodes draining the site of sensitization: (i) anti-oxazolone idiotype + B lymphocytes, found at day 3 after sensitization, transferred suppression to syngeneic recipients at the moment of their sensitization; (ii) anti-idiotype B lymphocytes, found at day 3 after sensitization, transferred suppression to syngeneic recipients when sensitization of these animals had been performed 3 days before cell transfer; (iii) T lymphocytes, found only at day 6 after sensitization, inhibited the passive transfer of contact sensitivity, indicating that they were effective on the efferent phase of the immune response. These results indicate that purified protein derivative from M. tuberculosis interferes with contact sensitivity by activating a complex and multiple immunoregulatory circuit.