The present study was conducted to determine the essential DNA sequences required for the transcription of the human phospholipid transfer protein gene. Truncation studies revealed that DNA sequences between -230 and -159, particularly those at the upstream region, were responsible for the full promoter activity. This region was able to compete with AP-2 and GRE oligonucleotides for the binding to HepG2 cell nuclear extract as shown by gel mobility shift assay. Further analysis, using site-directed mutagenesis, indicated that DNA sequences identical to Sp1 and highly homologous to GRE and Ap-2 consensus sequences were essential for the transcription. These findings support the concept that several elements, spread over the entire functional promoter, synergistically drive the basal transcription.