We have performed preoperative one-shot intra-arterial chemotherapy since 1976. However, in some cases, the results have not been satisfactory. Experimental studies were conducted to choose the drugs most suitable for this procedure. Drugs that were considered to be effective against bladder cancer, i.e., thio-TEPA, adriamycin (ADM), and cis-platinum (CDDP), were separately administered to groups of dogs via the common iliac artery or cephalic vein, and the concentrations of these drugs in the serum, bladder (mucosa and muscular layer), ileum, kidneys, and liver were measured 1 h later. The results revealed significantly high concentrations of intra-arterially injected ADM and CDDP in the bladder mucosa, suggesting that these drugs may be suitable for intra-arterial injection. It also appeared that thio-TEPA is unsuitable for this procedure. In clinical studies of 29 cases, preoperative one-shot intra-arterial injections were performed prior to total cystectomy or segmental resection of the bladder, and the effectiveness of the treatment was evaluated in terms of the histological effect, survival, and the relationship with the characteristics of the tumor. The results showed that the prognosis for cases showing therapeutic histological effectiveness (grade-IIb according to the classification of Shimosato et al.) was extremely good. Many patients in the grade-IIb group had stage-pT2 tumor or a tumor in the lateral wall. However, there seemed to be no significant differences between the drugs with respect to their histological effects.