We analyzed for alterations of the c-erbB-2 oncogene in 35 human stomach cancers and 8 cell lines derived from human stomach cancer. Amplification of c-erbB-2 was found in approximately 40% (5/13) of the tubular adenocarcinomas of the stomach examined, including 4 of 10 fresh tumors and one of 3 cell lines, but not in other histological types of stomach cancer examined (0/30), including 25 fresh tumors and 5 cell lines. This result strongly suggests that amplification of c-erbB-2 occurs frequently in tubular carcinomas in stomach cancer. Rearrangement of c-erbB-2 was also detected in one tubular adenocarcinoma. The rearranged fragment carried the 3' half, but not the 5' sequence, of the c-erbB-2 gene. Furthermore, one of the cellular homologues of v-erbA was amplified in 3 of 4 fresh tumors carrying the amplified c-erbB-2 gene. Both c-erbB-2 and the v-erbA homologue were expressed in all the stomach cancer cell lines tested.