Copper/zinc-containing superoxide dismutase (Cu/Zn SOD) is one of the essential enzymes that protects cells in aerobic conditions. To understand the mechanism of transcriptional regulation of the human Cu/Zn SOD gene, the proximal promoter region of Cu/Zn SOD has been investigated. In a previous study, it was found that transcription factors of the Sp1 and C/EBP family are associated with the expression of human Cu/Zn SOD [Seo et al. (1996). Gene, 178, 177-180]. Of the four known C/EBP activators, the effects of C/EBP alpha and C/EBPbeta on the transcription of Cu/Zn SOD were examined. Usually, one of the two C/EBP factors, C/EBP alpha or C/EBPbeta, exclusively stimulates the target gene, but, unexpectedly, C/EBP alpha and C/EBPbeta stimulated the expression of Cu/Zn SOD to a similar extent in our experiments. LIP, a dominant negative regulator of the C/EBP family, inhibited the transcriptional activation of Cu/Zn SOD stimulated by C/EBP alpha and C/EBPbeta. These results suggest that C/EBP alpha and C/EBPbeta can substitute each other and play similar roles on the transcription of Cu/Zn SOD.