AbstractTranscriptional activation studies involving the human oncoprotein and transcription factor Myc and its helix‐loop‐helix partner protein Max in mammalian cells are critical due to the presence of endogenous Myc and Max proteins. Here we show that co‐expression of the human c‐mycandmaxgenes from 2μ circle derived high copy number vectors in yeast cells stimulate the transcriptional activation of aLacZreporter gene fused to the yeast cytochrome‐c1, oxidase minimal promoter containing the adenovirus major late promoter element (AMLPE). The exchange of the single Myc binding site in the AMLPE by the two E‐box DNA motifs (CACGTG) present in the Myc responsive element of a human Myc target gene (ornithine decarboxylase) in front of a promoter‐reporter gene cassette results in a two‐fold enhanced ß‐galactosidase expression. Low expression ofmaxand high level expression of c‐mycat the same time led to a further enhancement of transcriptional activation from this promoter