A great diversity of antigens from Mycobacterium leprae have been described. One practical approach should be to utilize them as markers to indicate when a household contact is at risk of becoming infected and then moving to an active form of leprosy. For this purpose, sonic extracts of M. leprae were fractionated in 10% SDS-PAGE under reducing conditions. The fractionated proteins were then transferred to nitrocellulose sheets and incubated with sera from lepromatous leprosy cases, their contacts, and normal subjects in order to reveal the frequency of antigen recognition of each set of sera. The results showed that sera from lepromatous leprosy patients frequently recognized two proteins, one of approximately 28 kDa and the other of approximately 65 kDa, when compared with the sera from normal subjects. The contacts frequently recognized an approximately 16-kDa antigenic band, while sera from normal subjects recognized one protein of approximately 18 kDa. According to the results, the four recognized proteins from M. leprae can be considered markers of the above conditions (approximately 65 kDa, approximately 28 kDa for lepromatous leprosy, approximately 16 kDa for contacts, and approximately 19 kDa for normal subjects). From these, an easy serological test, such as an ELISA, can be developed to predict if a contact is moving toward lepromatous leprosy before detection of the actual clinical signs or symptoms.