The clinical presentation of visceral leishmaniasis shares similarities with other geographically specific infectious diseases associated with AIDS in terms of relapsing course and atypical presentation. However, visceral leishmaniasis has not, until now, been included in the AIDS case definition. The aim of this study was to describe the clinical features and determinants for relapse and case-fatality of visceral leishmaniasis in HIV-infected patients from a Spanish Mediterranean area. A chart review was conducted in 16 hospitals in the autonomous communities of Valencia and Murcia (Spain). From 1988 to 2001, a total of 228 episodes of visceral leishmaniasis were diagnosed in 155 HIV-infected patients by the detection of amastigotes in bone marrow aspirates or in other tissue samples. Most patients had advanced HIV disease, with a median CD4(+) lymphocyte cell count of 55 cells x 10(9) l, and 56% of them had a previous AIDS-indicator disease. The median duration of follow-up was 8.4 months. HIV-infected patients with visceral leishmaniasis presented with fever (76%), hepatomegaly (77%), splenomegaly (78%), and varying degrees of cytopenias. Leishmania was detected in atypical sites in 22 (14%) patients. A total of 37 (24%) patients had a relapse of visceral leishmaniasis. Female gender was a risk factor for relapse, whereas administration of secondary prophylaxis for visceral leishmaniasis and a completed therapy for visceral leishmaniasis were protective factors against relapse. A total of 86 (54%) patients died. Independent determinants for survival were CD4(+) lymphocyte cell count, completed therapy for leishmania, and secondary prophylaxis for visceral leishmaniasis. The findings show that, in HIV-infected patients, visceral leishmaniasis occurs in late stages of HIV disease and often has a relapsing course. Secondary prophylaxis reduces the risk of relapse. Visceral leishmaniasis in the HIV-infected population should be included in the CDC clinical category C for the definition of AIDS in the same way that other geographically specific opportunistic infections are included.