A reverse transcriptase-polymerase chain reaction (RT-PCR) method was adopted for detecting transcripts specific for retTPC/PTC, an activated form of the ret proto-oncogene reported to be found specifically in human papillary thyroid carcinomas. By this sensitive method retTPC/PTC transcript could be detected in about 500 fg of total RNA of TPC-1, a retTPC/PTC transcript-positive cell line. In Japanese patients, one of 11 papillary thyroid carcinomas, four of 19 follicular adenomas and one of two adenomatous goiters were positive for the transcript, indicating that the involvement of retTPC/PTC is not specific to papillary thyroid carcinomas. In several independent RT-PCR experiments using different portions of the same positive carcinoma tissue, retTPC/PTC transcript was always detected. On the other hand, the transcript was not always positive in different RNA samples from benign cases, suggesting that positive carcinomas are probably composed of clonal cell populations all expressing retTPC/PTC, whereas adenomas and adenomatous goiter comprise heterogeneous populations: both positive and negative for retTPC/PTC transcript. Activation of the ret proto-oncogene might therefore be involved in malignant conversion to thyroid carcinomas.