Glucose repression in the yeast Saccharomyces cerevisiae designates a global regulatory system controlling the expression of various sets of genes required for the utilization of alternate carbon sources. In a screen, designed for the selection of mutants with reduced glycolytic flux we obtained isolates which were shown by complementation of the cloned wild-type gene to be allelic to the glucose repression mutants grrllcat80lcot2 previously described. We demonstrate that the grrl lesion lead to a concentration-dependent decrease in glycolytic flux on glucose. It is very likely that this is caused by a significant decrease in the expression of various genes encoding hexose transporters (HXTI,3) leading to a reduced glucose-uptake rate. In contrast, expression of the maltose permease gene (MALll) and maltose utilization is normal. There is indirect evidence that grrl affects the uptake of amino acids, and others have shown that the sugar-induced transport of divalent cations is impaired. These effects are not glucose-specific. We suggest that Grrl, a putative cytoplasmic protein, has a central function in the sensing of nutritional conditions for a variety of unrelated substances, and that relief from glucose repression may be a corollary of this defect in sensing.In the yeast Saccharomyces cerevisiae glucose or other readily fermentable carbon sources act as global regulators of growth and metabolism. These regulatory effects are executed partly at the transcriptional level. Glucose repression and glucose induction designate mechanisms that exert specific control on glucose-sensitive genes. Glucose-repressible genes include SUC2 (invertase) and genes that are required for the utilization of alternate carbohydrates (the GAL, MAL and MEL regulons required for the utilization of galactose, maltose and melibiose, respectively; for review see [l]), mitochondrial genes [2] and nuclear genes for mitochondrial and gluconeogenic functions [3]. Analysis of glucose induction at the gene expression level is less advanced. Nevertheless, glucose or its metabolism exerts a plethora of activating effects on many cellular functions. It is not clear, in which way glucose repression and induction are functionally linked.Glucose repression mechanisms in S. cerevisiae have been revealed by means of appropriate mutants either defective in repression or in derepression (for review, see [4]). Analysis of individual mutants allowed in some cases the identification or localization of the regulatory defect. A number of such mutants lead to the identification of transcription factors or transcriptional regulators of glucose-sensitive genes. There are a number of mutants which apparently affect functions early in the signalling pathway for glucoseCorrespondence to