To elucidate the role of uptake transport proteins in tumor therapy, we performed expression studies and transport experiments with cytostatics on renal cancer cells RCC. Initially, we evaluated the expression of organic anion and cation transporters in the RCC. We observed no expression of OATs, OCT1 and OCT2, but a high expression of OCT3 in A498 cells, a low expression in LN78 cells and no expression in ACHN cells. We used these tumor cell lines to examine the interaction of OCT3 with cytostatics and the sensitivity of the cells to cytostatics. OCT3 mediated 1-Methyl-4-phenylpyridinium iodide(MPP) uptake and the inhibition potency of cisplatin and melphalan was tested. OCT3 transfected cells showed no inhibition by cisplatin, but melphalan inhibited MPP uptake by 50%. OCT3 stably expressing cells were more sensitive to melphalan than mock cells as examined by [3H]thymidine incorporation. Melphalan treatment of renal tumor cells revealed a 40% higher sensitivity in OCT3 expressing A498 cells than in ACHN cells. To extend our study on uptake transporters, we examined the expression of equilibrative nucleoside transporters 2 (ENT2) in RCC. We measured the [3H]gemcitabine uptake in LN78, which express ENT2 and A498 cells, which do not express ENT2. LN78 cells have a 4 fold higher gemcitabine uptake than A498 cells and show 50% increased sensitivity to gemcitabine than A498 cells. These results document a higher cytostatic effect on cells expressing specific uptake transporters.