Intravesical bacillus Calmette-Guérin is a highly effective therapy against superficial bladder cancer recurrences and urothelial carcinoma in situ, the antitumoral effects of which seem to be linked to immunological effector mechanisms. To characterize further these mechanisms which contribute to the long-term effectiveness of BCG therapy, the local mononuclear cell subsets as well as the local cytokine production were assessed in the bladder wall of patients receiving intravesical BCG immunotherapy with special regard to long-term persisting changes, using immuno-enzymatical staining methods. All patients exhibited a significant increase after BCG in the local mononuclear cell population, with a predominance of the helper T-cell subset. Immunocompetent cells expressed activation markers for a prolonged period. Furthermore, a significant increase in the local cytokine production after the initial course of BCG was demonstrable, which persisted even after 12 to 21 months. These changes suggest that the BCG-induced activation of the local immune system persists over a long period after an initial course of intravesical therapy.