Ionizing radiation is a well known risk factor of thyroid cancer development, but the mechanism of radiation induced carcinogenesis is not clear. The RETPTC oncogene, an activated form of the RET proto-oncogene, is frequently observed in papillary thyroid carcinoma (PTC); RETPTC1,-2 and-3 are known to be the three major forms. High frequencies of RETPTC rearrangements have been observed in radiation-associated PTC, such as those appearing post-Chernobyl or post-radiotherapy, but the rearrangement types differ between these two populations. We investigated whether a specific type of RETPTC rearrangement was induced by X-rays in vivo and in vitro. In human normal thyroid tissues transplanted in scid mice, the RETPTC1 rearrangement was predominantly detected throughout the observation period (up to 60 days) after X-ray exposure of 50 Gy. On the other hand, RETPTC3 was detected only 7 days after X-irradiation, and no transcript of RETPTC2 was detected. These results are supported by the results of an in vitro study. The RETPTC1 rearrangement was preferentially induced in a dose-dependent manner by X-rays within a high dose range (10, 50 and 100 Gy) in four cell lines. On the other hand, RETPTC3 was induced at a much lower frequency, and no induction of RETPTC2 was observed. These results suggest that the preferential induction of the RETPTC1 rearrangement may play an important role in the early steps of thyroid carcinogenesis induced by acute X-irradiation.