OBJECTIVE To evaluate the cellular and humoral immune responses after oral hormone therapy in postmenopausal women. Study design This was a prospective cohort study, with intervention. The main outcome measures were delayed-type IV cell-mediated hypersensitivity, leukocytes, immunoglobulins, interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS The delayed-type cell-mediated hypersensitivity was measured by using five common allergens before and after 3 months of hormone therapy. Each type of leukocyte cell was counted before and after hormone therapy. Different subtypes of lymphocytes were determined by flow cytometry. Immunoglobulins G, A and M were measured by nephelometry; immunoglobulin E was measured by electrochemiluminescence. IL-6 and IL-10 concentrations were determined by chemiluminescence. RESULTS Hormone therapy increased the response to tuberculin antigen without changing the total number of leukocytes, eosinophils, neutrophils, lymphocytes, and CD4 +, CD8 + B cells. Both monocyte number and CD4 + /CD8 + ratio suffered a slight modification (p = 0.057). Immunoglobulins A, M and E remained unchanged and immunoglobulin G decreased (p = 0.029). IL-6 levels remained stable but IL-10 concentrations increased significantly after hormone therapy. CONCLUSIONS Short-term oral hormone treatment has no impact on the cellular immune response but, concerning the humoral immune response, immunoglobulin G decreased and the levels of IL-10 were significantly higher.