One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.