Histological analysis of human leprosy periapical granulomas was conducted to study the histological responses to Mycobacterium leprae, Many Langhans-type giant cells and epithelioid cell tubercles were observed, although M. leprae were not detected in leprosy periapical granulomas, Although numerous T- and B-cells were infiltrated in leprosy periapical granuloma, the T-/B-cell ratio of leprosy is not changed to that of periapical granulomas isolated from normal patients, These findings suggested that human leprosy periapical granulomas develop as a result of immunological responses to M. leprae.