Objectives: Hepatitis B virus (HBV) infection is effectively preventable by immunization with the commercially available recombinant HBV vaccines (HBVvac) in approximately 95% of healthy people. Immunosuppressive diseases like hematological malignancies are a risk factor for non-response to HBVvac. The aim of this study was to determine the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant in lymphoproliferative disorders (LPD). Patients and Methods: One- hundred and two patients with LPD were randomized to receive either a single dose of 40 mu g HBVvac intramuscularly or one course of 40 mu g HBVvac after 5 mu g/kg recombinant GM-CSF injection. Results: Of the 94 patients that could be evaluated at 1 month, the seroprotection rate was higher in GM-CSF + HBVvac group (25.5% in GM-CSF + HBVvac group vs. 17% in HBVvac group). The median anti-HBs titer was also higher in GM-CSF + HBVvac group. However the difference did not reach to a significant level in terms of response rate and median antibody titers (P > 0.05). Univariate analysis identified age and time to vaccination from the last chemotherapy course as significant predictors of seroprotection. In multivariate analysis, age was the only predictor of achieving a seroprotective response. Patients who lost the seroprotective response during monitoring were boosted with a 20 mu g HBVvac and they all achieved a seroprotective anti-HBs titer > 100 mIU/mL. Conclusion: In LPD, the response to HBVvac is impaired. GM-CSF enhance to HBVvac in terms of the rate of response and average of antibody titers at the dose and schedule given.