A positive Mitsuda skin test for delayed type hypersensitivity to Mycobacterium leprae is associated with a high level of protection against lepromatous leprosy, while the value of tuberculin sensitivity in leprosy is less pronounced. Cutaneous lymphocytes, isolated from the Mitsuda reaction of a PPD-positive individual not previously exposed to M. leprae, were cloned with Dharmendra lepromin and analysed for antigen specificity. Thirteen lepromin-responsive cell lines were derived, with greater than 95% certainty that the number of true clones was at least five and the number of functionally monoclonal lines at least seven. All lepromin-responsive clones proliferated in response to PPD as well, implying that PPD-responsive cells can fulfill the helper T cell function required for the in vivo Mitsuda reaction.