Reactivation of hepatitis is one of the most serious complications of chemotherapy in lymphoma patients who are carriers of the hepatitis B virus (HBV). Glucocorticoids are linked to increased risk of HBV reactivation. This study seeks to clarify whether removal of glucocorticoids from chemotherapy regimens may decrease the risk of HBV reactivation. Eligible patients were seropositive for hepatitis B surface antigen (HBsAg) and had histologically proven non-Hodgkin's lymphomas for which intensive chemotherapy was indicated. Patients were randomized to receive either ACE (epirubicin, cyclophosphamide, and etoposide) or PACE (prednisolone + ACE). A total of 50 patients were enrolled, 25 each for the ACE and PACE arms. The cumulative incidence of HBV reactivation at 9 months after starting chemotherapy was 38% and 73% for ACE and PACE arm, respectively (P =.03). The degree of clinical hepatitis was significantly more severe in the PACE arm: 11 patients (44%) in the PACE and 3 patients (13%) in the ACE arm had ALT elevation more than 10-fold of normal (P =.025), and 7 patients (28%) in the PACE and 1 patient (4%) in the ACE arm had icteric hepatitis (P =.049). Complete remission of tumors occurred in 11 (46%) patients in the PACE and 8 (35%) patients in the ACE arm (P =.556). The estimated overall survival rate at 46 months was 68% in the PACE arm and 36% in the ACE arm, respectively (P =.18). In conclusion, steroid-free chemotherapy decreases the incidence and severity of HBV reactivation in HBsAg-positive lymphoma patients. However, further research is needed to evaluate whether steroid-free chemotherapy may confer a less satisfactory control of lymphoma.