The CIF1 gene (also called GGS1/TPS1) encodes a protein of the trehalose synthase complex that affects trehalose accumulation and general glucose sensing by Saccharomyces cerevisiae cells. There is considerable debate as to whether CIF1-dependent trehalose accumulation is a determinant in heat shock-acquired thermotolerance. Thermosensitivity of cif1 mutants could alternatively, or also, be related to gene expression-signalling defects in such strains. Because many signal-dependent factors are involved in stress protection and repair in yeast, we have compared the expression of various stress response and heat shock genes in 'isogenic' CIF1 and cif1 strains growing exponentially in galactose medium. Transcription of CTT1, CIF1, HSP26, HSP82, HSP104, SSA4 and UB14 was notably lower in the cif1 mutant following heat shock. Moreover, a single copy of chromosomally integrated HSP104-lacZ fusion gave up to 5.5-fold more heat shock induction in the CIF1 strain compared to the cif1 mutant. We conclude that reduced heat shock-acquired thermotolerance in cif1-deletion mutants growing exponentially on galactose is more likely to result from a general reduction in expression of stress response and heat shock genes, than simply or solely through deficiency of trehalose accumulation. The possible role of CIF1 in modulating stress response is discussed.