Exposure to ionizing radiation has long been well-recognized as a risk factor for cancer development. Since ionizing radiation can induce mutations, an accurate way of measuring somatic mutation frequencies could be a useful tool for evaluating cancer risks. In the present study, we have examined in vivo somatic mutation frequencies at the erythrocyte glycophorin A (GPA) and T-cell receptor (TCR) loci in 18 Thorotrast patients who have been continuously irradiated with alpha-particles emitted from the internal deposition of thorium dioxide and who thus have increased risks of certain malignant tumors. When compared with controls, the results showed a significantly higher frequency of mutants at the lymphocyte TCR loci but not at the erythrocyte GPA loci in the Thorotrast patients. The discrepancy between the results of the two assays is discussed.