Heat shock factor (hsf) is the transcriptional activator that governs the transcriptional response of eukaryotic cells to stressful conditions. The structure and regulation of hsf is highly conserved. We describe deletion mutations in hsf+ that alter the ability of Schizosaccharomyces pombe to respond to different stressful conditions. One mutation causes increased sensitivity to cadmium while maintaining near normal sensitivity to heat stress, while another mutation confers increased sensitivity to heat stress but retains normal sensitivity to cadmium. Despite the differential sensitivity of these two strains to cadmium and heat stress, the mutant hsf proteins in each strain were activated by both cadmium and heat. However, we found that these mutations differentially affected the ability of hsf to activate different promoters: one mutated hsf activated the ssp1+ gene better than the wis2+ gene following either stress, while the other mutated hsf activated wis2+ better than ssp1+. We propose that the differential ability of strains that contain these mutant hsfs to survive cadmium and heat stress is not caused by differences in activation of hsf, but is caused instead by differential abilities of the mutant hsfs to activate the appropriate sets of genes needed for survival.