The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.