To provide further data on the possible applications of the single cell gel electrophoresis (SCGE) or Comet assay in human biomonitoring studies, we have evaluated the eventual genetic damage induced by therapeutic exposure to 131I, by measuring the tail length of the comet and the amount of DNA damage in peripheral blood cells from 16 hyperthyroidism patients treated with [131I]sodium iodide by oral administration. Blood samples were taken just before the treatment and 1 week and 1 month after. The results show a slight but significant increase in the mean tail length in the sample obtained 1 month after treatment. When the cells were classified according to the grade of damage the two post-treatment samples showed a clear increase in the proportion of damaged cells. The results of this study indicate that the DNA damage caused by 131I can be detected with the Comet assay, but when comparing the data reported here with our previous results obtained from the same patients and sampling times with the sensitive and well-established micronucleus test, the response in the Comet assay was less clear.