Until recently, interest in human complement receptor type I (CR1) has focused on immune complex processing, which contributed to our understanding of regulatory mechanism of complement activation. However, the promoter structure and transcriptional regulation of human CR1 gene has not been clear. To study the unique regulation of human CR1 gene expression, we assessed promoter activity of the 5'‐flanking region of human CR1 gene using transient transfection and gel mobility shift assays. In this study we demonstrated that NF‐Y binds to the inverted CCAAT element and that the functional interaction with protein(s) which bind to the GC‐rich motif may be necessary for optimal transcription of human CR1 gene. We also show that sequence elements which located at ‐95/‐58 and +45/ +50 are important for optimal transcription of CR1 gene.