Radionuclide study has not been frequently applied to pancreatic cancers because of the absence of suitable radiopharmaceuticals for their positive depiction. We evaluated thallium-201 chloride (201T1) SPECT for the investigation of pancreatic cancers. The subjects included 24 patients with pancreatic cancer, seven with benign disorders and 10 controls. Each patient fasted prior to the examination for more than 12 hr, and 201T1 SPECT was obtained 10 min after the injection of 148-222 MBq of 201T1. When the boundary of tumor uptake of 201T1 was unclear because of the adjacent physiological liver activity, subtracted SPECT using 99mTc-phytate was performed to clarify it. 201T1 did not accumulate in the pancreas of the controls. In contrast, of the 24 pancreatic cancers, 21 demonstrated positive uptake, for a sensitivity rate of 87.5%, and the mean tumor/liver ratio was 0.76 +/- 0.16 (range, 0.58-1.28). Abnormal uptake was also noted in three of the seven benign disorders, but with a comparatively lower lesion/liver ratio (range, 0.35-0.51). 201T1 activity per mg tissue in the resected specimens of two patients with pancreatic cancer revealed higher activity in the tumor than in normal parenchyma. 201T1 uptake in the five conservatively treated pancreatic cancers showed alteration similar to the serum level of tumor markers. These results suggest that 201T1 SPECT may have clinical potential for investigating pancreatic cancers as well as for the monitoring of treatment effect.