The kinetics of uptake and retention of Tl-201, Rb-86, and K-42 and -43 have been studied in cultured mammalian cells and related to their radiotoxicities. Among the four radionuclides, the intracellular localization of Tl-201, the only emitter of Auger electrons, was important for the manifestation of its cytocidal effects. The results have been found consistent with the short-range nature of Auger electrons and are substantiated by our theoretical dosimetric calculations. The possible implications of this in vitro system for applications of Tl-201 in nuclear medicine are indicated.