Enzymes in diverse amino acid biosynthetic pathways in Saccharomyces cerevisiae are subject to a general amino acid control in which starvation for any amino acid leads to increased levels of the mRNAs encoding these enzymes. The short nucleotide sequence TGACTC, found nontandemly repeated upstream from the coregulated structural genes, serves as a cis-acting site for positive regulation of transcription. Multiple trans-acting repressors and activators have been identified. Most of these factors act indirectly by regulating the level of an activator encoded by the GCN4 gene. This regulation occurs at the level of GCN4 translation and is mediated by sequences in the long 5' leader of GCN4 mRNA. The GCN4 protein is the most likely candidate for the transcriptional activator that interacts with the TGACTC sequences at the structural genes.