185 Long-term prophylaxis with hepatitis B immune globulin (HBIg) has been shown to reduce hepatitis B (HBV) recurrence and to improve survival in HBsAg positive liver transplant recipients. “High dose” HBIg - up to 10,000 IU (≈40 ml) monthly - is utilized in most protocols. The cost of this therapy, however, is prohibitive and the supply of HBIg is at times limited. Aim: To report on our prospective study using“low dose” HBIg immunoprophylaxis to prevent HBV recurrence after orthotopic liver transplantation (OLT) in HBsAg positive patients.Methods: All HBsAg positive patients received 100 ml HBIg (1 ml≅ 265 IU HBsAb) IV intra-op, followed by 5 ml IM X 7 days post-op. Thereafter, 5 ml were administered IM as needed to maintain HBsAb serum concentration > 100 IU/1. HBsAb titer was checked regularly to determine a stable dosing schedule for each patient. HBIg therapy was discontinued if HBsAg and/or HBV DNA reappeared.Results: Between 3/93 and 6/97, 20 HBsAg positive patients underwent OLT. 2 HBeAg positive patients who failed to clear HBsAg post-op did not receive maintenance HBIg. The remaining 18 patients (9 HBeAg and/or HBV DNA positive; 9 HBeAb positive) cleared HBsAg and received maintenance therapy. Median time required to arrive at a stable dosing schedule was 2 months (range 0.5-11.7 m): 5 ml HBIg was given q 4 weeks to 14 patients. The stable frequency for others was q 1.5, 2, and 3 w. Total HBIg used for each patient was 218 ml (171-636 ml) during the first year and 65.2 ml (65-92 ml) during second and each subsequent year. Median follow up to date is 33 m (6-58 m). Recurrent HBV developed in 4 of 18 patients (22%) at 12, 16, 16, and 49 m after OLT. All these patients were HBeAg and/or HBV DNA positive. None of the HBeAb positive patients developed recurrent HBV. Recurrence was due to noncompliance in 2 and chemotherapy for cloacogenic carcinoma in 1 patient. A single patient died of complications of metastatic hepatocellular carcinoma after 6 m. HBIg was well tolerated: pain at the injection site was the only complaint.Conclusions: a) The overall rate of HBV recurrence after OLT (22%) observed using this low dose protocol compares favorably to published “high dose” rates of recurrence. b) Most of the patients(82%) received HBIg at a stable, q 4 week dosing interval derived by maintaining a target HBsAb titer > 100 IU/1. c) The low dose prophylaxis was well tolerated. d) Breakthroughts in HBcAg positive patients were primarily due to noncompliance. “Low dose” HBIg prophylaxis, therefore, is effective in both HBeAb and HBeAg positive patients and has the potential for substantial cost savings and conservation of a scarce resource.