The toxicity of uranium to several isolates of Thiobacillus ferrooxidans was determined. Plasmid DNA of approx. 13±0.5 megadaltons was detected in four cultures that exhibited the highest resistance to UO2 2+. One isolate, TFI-7, always contained a 13 megadalton plasmid and was always resistant to uranium. Another isolate, TFI-13, showed increased resistance to uranium only after a long lag period during which the cell numbers declined 1000-fold when uranium was added to the medium. The surviving TFI-13 population was able to grow with no further loss of viability upon re-exposure to uranium and it contained a 13 megadalton plasmid. Upon subculture in the absence of uranium this resistance declined. Concurrent with the loss of uranium resistance, the 13 megadalton plasmid could no longer be detected. Attempts to cure plasmids by elevated temperatures and chemical agents were unsuccessful.