Objective: The aim of the study was to evaluate the role of vitamin B12 in patients with pernicious anemia. Materials and Methods: This study was conducted prospectively at the Turgut Özal Medical Center, Department of Hematology, between April and November 2002. Absolute numbers and ratio of the surface antigens of T and B lymphocyte subgroups, CD4/CD8 ratio were calculated in order to evaluate changes in leukocyte and lymphocyte numbers; natural killer (NK) cell count, serum C3, C4, and levels of immunoglobulins G, A, and M were also measured to evaluate vitamin B12 effect on immunity. Values obtained before treatment with cyanocobalamin were compared with those found during peak reticulocyte count. Results: In vitamin B12-deficient patients, absolute numbers of CD4+ and especially CD8+ lymphocytes were found to be decreased; CD4/CD8 ratio increased, and NK cell activity was depressed. After cyanocobalamin treatment, absolute numbers and percentage of lymphocyte subgroups were elevated. Increased CD4/CD8 ratio and depressed NK cell activity were restored and levels of C3, C4, and immunoglobulins were elevated. Conclusion: These findings suggest that vitamin B12 has important immunomodulatory effects on cellular immunity, and abnormalities in the immune system in pernicious anemia are restored by vitamin B12 replacement therapy.