The Leishmania P2 proteins have been analyzed as potential tools for the immunodiagnosis of human mucocutaneous and visceral leishmaniasis. Two recombinant Leishmania infantum proteins, rLIP2a and rLip2b, were used. The analysis indicated that the rLiP2a and rLiP2b proteins are recognized by 76% (16 of 21) and 42% (9 of 21), respectively, of sera from patients with mucocutaneous leishmaniasis and by 50% (5 of 10) and 40% (4 of 10), respectively, of sera from patients with visceral leishmaniasis. The Leishmania P2 proteins were engineered to have deletions of particular amino acids from the carboxyl-terminal region in order to avoid cross-reactivity with sera from patients with systemic lupus erythematosus and Chagas' disease, since it is known that this region is the main target of the autoantibodies present in sera from these patients. The results show that while the modified recombinant proteins rLiP2a-Q and rLiP2b-Q, in which the five carboxyl-terminal amino acids had been deleted, maintain the leishmaniasis-specific epitopes, they do not react with sera from patients with autoimmune disease and Chagas' disease. For this reason, and also because the sera from patients with tuberculosis and leprosy, diseases that have to be considered in a differential clinical diagnosis of infectious diseases, do not react with the rLiP2a-Q or rLiP2b-Q protein, we think that the engineered proteins may be considered specific tools for the immunodiagnosis of mucocutaneous and visceral leishmaniasis.