The influence of high energy shock waves (HESW) on the local concentration of systemically given TNF-alpha was studied in a syngeneic rat bladder tumor model. 125I-TNF-alpha was injected intravenously and within 1 minute was followed by HESW tumor exposure. High energy shock waves were generated using an experimental shock wave emitter based on the Siemens Lithostar Plus. Administration of HESW to RBT323 tumors resulted in a 3-fold increase in uptake of 125I-TNF-alpha in the tumor compared with nontreated tumors, whereas the tissue distribution and pharmacokinetics of nontumor tissue were similar irrespective of HESW exposure. These results demonstrate that HESW administration leads to an increase in the local concentration of a systemically given drug. The capacity of HESW to increase local drug concentrations will be of importance in designing more effective combined treatment strategies.