Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive K+-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Balb/c mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. 100 μg of pinacidil dissolved in 200 μl DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq (5 μCi) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice (58±4%), than in the control group (67±3%) at 24 hours after with injection of 100 μg pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice. (Korean J Nucl Med 2000;34:303-11)