Local immunotherapy with bacillus Calmette-Guerin (BCG) can prevent recurrences and progression of superficial bladder cancer, but the antitumoral mechanism of BCG is still unclear. The first event seems to be binding of BCG to urothelial cells via fibronectin, and processing of mycobacterial antigens by antigen-presenting cells. Experimental data suggest that bacterial antigens can also be processed by urothelial cells. CD4 lymphocytes subsequently recognize antigenic peptides presented by HLA class II molecules. The most common profile of urinary cytokines is interleukin-2 and interferon-gamma, suggesting the predominant involvement of the Th1 lymphocyte subpopulation. Natural killer cells, lymphocyte-activated killer cells, BCG-activated killer cells and macrophages are able to kill bladder tumor cells in vitro, but there is no evidence that a major histocompatibility complex (MHC)-restricted specific T cytotoxic response is involved in BCG antitumor activity.