In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl2, both in rats and human volunteers. Absorption of oral SnCl2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloride. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of 99mTcO4- in rats that were fed 5 mg of stannous chloride (3.13 mg Sn2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl2. We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m--such as the amount of orally administered SnCl2, the time of injection of radionuclide after oral SnCl2, and the optimum time for the imaging.