PURPOSE: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. METHODS: Therapeutic effects of MPD was also evaluated in 58 patients (49 females and 9 males, mean age 50±11 years) of papillary thyroid cancer. Among them 43 patients were treated with ≤7.4 GBq, while 15 patients with ≥9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. RESULTS: MPD measured by CF method using tracer and therapeutic doses were 13.3±1.9 and 13.8±2.1 GBq, respectively (P=0.20). They showed a significant correlation (r=0.8, P<0.0001). Exposed doses to blood measured by CF and biological methods were 1.54±0.03 and 1.78±0.03 Gy (P=0.01). They also showed a significant correlation (r=0.86, P=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (P=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, P=0.46). CONCLUSIONS: measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.