The expression of the transcription factor Sp1 and EGF receptor (EGFR) was examined on human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding normal mucosa in order to clarify the mechanism of overexpression of EGFR gene without gene amplification. All 7 carcinoma cell lines expressed Sp1 mRNA, the levels of which were closely correlated with the expression of EGFR mRNA except for one cell line. The gel retardation analysis revealed that the levels of Sp1 mRNA were parallel to its DNA binding activities. In 18 surgical cases, 12 tumors expressed Sp1 mRNA at higher levels than normal mucosa. The cases with overexpression of Sp1 showed the high level of EGFR mRNA. These results suggest that overexpression of Sp1 in tumor cells may induce overexpression of EGFR without gene amplification in human gastric carcinomas.