The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.