The Xin vitroX activation by glucose of the RAS-adenylate cyclase system in membranes from a strain of Saccharomyces cerevisiae lacking any functional glucose kinase activity presents similar features to those of the wild type. However, this triple mutant appears to be unable to produce the glucose-induced increase of cAMP levels Xin vivoX. The results obtained in vitro indicate that the signal transduction mechanism is active in the mutant cells and suggest that the absence of intracellular acidification in vivo might be responsible for the lack of response to glucose.