A computer-aided pattern search of the entire yeast genome was designed and used to identify 186 putative stress response element-regulated genes in Saccharomyces cerevisiae. Transcript levels of eight of these candidate genes were examined, and three (37%) were shown to be heat shock- and DNA damage-inducible and to require the Msn2p and Msn4p transcriptional activators for stress regulation. Significantly, several heat shock protein (HSP) genes were identified in this computer search. Using a series of single and multiple regulatory mutants, we demonstrate unexpected regulatory complexities among the HSP genes from S. cerevisiae following heat shock.