Given the central role of protein synthesis in cellular function, it is likely that intricate mechanisms exist to detect and respond to amino acid deprivation. However, the current understanding of amino acid-dependent control of gene expression in mammalian cells is limited. A few examples of enzyme, transporters, and unidentified mRNA species subject to amino acid availability have been reported and some examples are summarized here. Each example chosen-asparagine synthetase, system A transport activity, and ribosomal protein L17--are associated with different aspects of amino acid metabolism, and therefore reflect the spectrum of metabolic pathways influenced by substrate control. Most of the data accumulated thus far suggest that a general control response exists such that these various activities are induced when any one of several amino acids becomes limiting. Consistent with observations in yeast, it appears that the degree of tRNA acylation and its resultant effect on protein synthesis may play an important role in initiating the starvation signal. De novo protein synthesis is required for starvation-dependent increases in several mRNA species, which suggests that the amino acid signaling pathway is composed of a series of intermediate steps before activation of specific structural genes.