The characteristics of two cases of histoplasmosis in AIDS patients in our institution are presented together with a review of the 11 cases published in Spain since 1988 in addition to the current knowledge on histoplasmosis in patients with human immunodeficiency virus infection (HIV). In all except 2 of the 13 patients there was epidemiologic history of a stay in a country in which histoplasmosis is endemic. The 12 cases described in which this information is available had CD4 counts under 100/microL. The clinical manifestations of presentation were fever (92.3%) associated or not with other unspecific symptoms (asthenia, anorexia, cough, diarrhea) with a subacute course of two or three months. Physical examination demonstrated hepatosplenomegaly in 76.9% of the cases and 61.5% of the patients presented cutaneous lesions. Thoracic radiography was abnormal in 55% (61.5% had respiratory symptoms). Diagnosis was achieved by isolation of the fungus in the cutaneous biopsies in all the patients with dermatologic involvement and in 7 cases identification was performed in the bone marrow. In all the cases induction treatment was with anphotericin B and in those who reached the maintenance phase itraconazol was used in 7 cases and ketoconazol in one case. None of the patients treated with itraconazol, including the two in our center, presented recurrence at the time of completion of follow up. In conclusion, histoplasmosis is frequently presented as a prolonged febrile syndrome with unspecific characteristics, thus emphasizing the importance of including travel history to other countries in the anamnesis. The increase in journeys to endemic countries and immigration from these areas had led to an increase in the number of cases of histoplasmosis in patients with HIV infection in Spain.