We analysed factors associated with moderate to severe acute GVHD in 111 patients treated with fludarabin-based reduced intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). Most patients had a haematological malignancy. Donors were 97 HLA-A, -B and -DRbeta1 identical unrelated and 14 HLA-A, -B or -DRbeta1 allele mismatched unrelated donors. In the univariate analysis, we found ten factors associated with acute GVHD. These were diagnosis (P=0.06), GVHD prophylaxis with combinations other than CsA+MTX (P=0.006), graft nucleated (P<0.001) and CD34 (P<0.001) cell-dose, bidirectional ABO mismatch (P=0.001), conditioning (P=0.002), hospital vs home-care (P=0.06), ATG dose (P<0.001), donor herpes virus serology (P=0.07) and an immunized female donor to male recipient (P=0.05). In the multivariate analysis, three factors remained significant: a high CD34 cell dose (P<0.001), low dose (4 mg/kg) ATG (P<0.001), and an immunized female donor to male recipient (P<0.01). Patients receiving a CD34 cell dose > or =17.0 x 10(6) per kg had a higher incidence of GVHD, 53.7%, compared to 22.3% in patients receiving a lower dose (P=0.002). In patients without any of these risk factors (n=70), the incidence of acute GVHD was 14.1%, while it was 38.0 and 85.0% in patients with one (n=29) or two (n=10) risk factors (P<0.001). We concluded that risk factors for acute GVHD using RIC are similar as using myeloablative conditioning.