This report describes epidemiological, clinical and laboratorial aspects of 111 cases of disseminated histoplasmosis from Rio Grande do Sul over a 25-year period (1977-2002). AIDS and non-AIDS patients were analyzed was the predisposing disease in 63.1% of the patients. In both groups there were mostly men, without evidence of exposure to microfoci contaminated with Histoplasma capsulatum. The main clinical features were systemic (fever and weight loss were present in 97.1 and 92.7% of AIDS and non-AIDS cases), followed by respiratory and mucocutaneous manifestations. Seromycology (positive in 54.5% and 65.3% in AIDS and non-AIDS cases) was useful as a screening test. The high index of cutaneous involvement in AIDS patients (44.3%) compared with North American reports (p <0.01) suggests that different strains of Histoplasma capsulatum may induce different clinical manifestations of the same disease.