Risk factors for invasive aspergillosis (IA) are incompletely identified and may undergo changes due to differences in medical practice. A cohort of 189 consecutive, adult patients with neutropenia hospitalized in the hemato-oncology ward of the University hospital Berne between 1995 and 1999 were included in a retrospective study to assess risk factors for IA. In total, 45 IA cases (nine proven, three probable, 33 possible), 11 patients with refractory fever and 133 controls were analyzed. IA cases had more often acute leukemia or myelodysplastic syndrome (MDS) (88 vs 38%, P < 0.001) and a longer duration of neutropenia (mean 20.6 vs 9.9 days, P < 0.001). They also had fewer neutropenic episodes during the preceding 6 months (mean 0.42 vs 1.03, P < 0.001), that is, confirmed (82%) and probable (73%) IA occurred most often during the induction cycle. A short time interval ( < or = 14 days) between neutropenic episodes increased the risk of IA four-fold (P = 0.06). Bacteremia, however, was not related to the number of preceding neutropenic episodes. Therefore, neutropenic patients with leukemia or MDS have the highest risk of IA. The risk is highest during the first induction cycle of treatment and increases with short-time intervals between treatment cycles.