Leishmania amazonensis is a major etiological agent of human cutaneous leishmaniasis in the Americas; nevertheless there are some reports of this species causing visceral disease in dogs and men. In the present work we have studied a Leishmania strain isolated from a human case of visceral leishmaniasis. We have infected different mouse strains and analyzed the development of the disease, studying the parasite's ability to visceralize and whether this ability is influenced by host genetics. Female BALB/c, C57BL/6, C57BL/10, CBA, DBA/2, and C3H/He mice were subcutaneously infected with 10(4) L. amazonensis amastigotes. BALB/c, C57BL/6 and C57BL/10 mice were found to be very susceptible to infection, showing lesions that developed to necrosis and ulceration. CBA mice developed a late but severe lesion. DBA/2 mice developed only discrete lesions, while C3H/He mice did not develop any lesions. All mouse strains except C3H/He showed some degree of visceralization, presenting parasites in the spleen, while BALB/c, C57BL/6 and CBA presented parasites also in the liver. Moreover, most of the strains presented high parasite load at the infection site, whereas DBA and C3H/He mice showed low or no parasite load 90 days after infection, respectively. Histopathology corroborates the results, showing that susceptible mice presented an inflammatory reaction with parasites in the skin, lymph nodes and spleen, while strains that are more resistant presented low parasitism and discrete inflammatory reaction. Results indicate that this isolate is extremely virulent, can easily visceralize and that the pathogenesis of leishmaniasis is, at least in part, related to the genetic background of the host.