BACKGROUND: It has been reported that repeated intravenous injections of a relatively large amount of Leishmania amazonensis amastigote extract (LaE) in BALB/c mice exacerbates the infection of these mice by Leishmania braziliensis. The identification of the extract active principle(s) through physicochemical purification often involves dilution and losses of protein in the course of successive purification procedures. The large amount of the extract required to induce the phenomenon, therefore, hinders the carrying out of experiments aimed at identifying the active molecule(s) through extract purification. In the present work, a dose-response experiment was done to find out if smaller amounts of LaE than that necessary to be used by the intravenous route would reproduce the phenomenon when injected by the intradermal route. In addition, it was also investigated whether a Leishmania braziliensis amastigote extract (LbE) would exert the same effect and whether the effect would occur in C57BL/6 mice. RESULTS: It was found that a single injection of either LaE or LbE containing 5 µg of protein was capable of enhancing the infection in BALB/c but not in C57BL/6 mice. In addition, it was observed that the largest tested doses of LbE (containing 30 and 180 µg of protein) failed to enhance the infection by L. braziliensis, whereas all doses of LaE enhanced equally that infection. CONCLUSIONS: Those results indicate the possible existence in LbE, and not in LaE, of molecules that interfere with the extract infection-enhancing activity when it is injected in large amounts, and that the inoculation of Leishmania extracts through the intravenous and intradermal routes potentiate the infection by L. braziliensis through the same mechanism.