The promoter regions of the clustered human spermatid-specific nucleoprotein PRM1, PRM2 arid TNP2 genes were compared to define regulatory elements that may govern their expression. Sequence alignment revealed two wll conserved motifs, despite a lack of extensive homology. They are located at similar positions within the first 400 nt of their 5' UTRs. Conservation of these motifs may reflect selective evolutionary pressure to maintain their structure. This supports the view that these elements assume a central role in the coordinate regulation of this gene cluster during spermiogenesis. The distribution of binding sites of known transcription factors was also assessed within the regions flanking the 5' ends of these genes. This analysis should prove useful in directing studies that define the signals necessary for the coordinate regulation of this spermatid specific gene cluster.