Two cell lines of human embryonal carcinoma, Tera-1 and Tera-2, have been found to exhibit a 4- to 6-fold amplification of protooncogene c-Ki-ras2. The polyadenylic acid selected RNA also showed 8-fold or greater enhancement, showing marked elevation in the level of two major mRNAs, 5.7 and 4.0 kilobases, and two additional minor mRNAs, 2.3 and 1.2 kilobases, as compared with those of a normal human embryonic fibroblast cell line, MRC-5. More than one-half of the number of tumor samples obtained from metastatic human embryonal carcinomas also showed c-Ki-ras2 gene amplification and enhanced mRNA expression. However, the c-Ki-ras2 gene amplification did not always lead to enhanced mRNA expression, and some embryonal carcinomas showed mRNA overexpression without apparent c-Ki-ras2 gene amplification. These results suggest that human embryonal carcinomas may have c-Ki-ras2 amplification and/or overexpression before in vitro culture. Among various chromosomal changes observed in Tera-1 and Tera-2 cells, there were anomalies in chromosome 12 in which c-Ki-ras2 is located although these karyological changes alone could not account for the amplification observed. It is suggested that the genomic instability and active DNA replication during the early developmental period may give rise to changes involving c-Ki-ras2 which may contribute to oncogenic processes.