The effect of various sulfhydryl compounds on the survival of exponentially growing monolayer cultures of Chinese hamster cells (HA1) heated to temperatures of 37-43 degrees was examined. Concentrations of cysteamine which were nontoxic or minimally toxic at room temperature or 37 degrees became increasingly toxic at elevated temperatures, greatly potentiating the killing produced by heat alone in the absence of cysteamine. This enhancement of hyperthermia-induced cell killing increased with increasing cysteamine concentration, increasing duration of cysteamine exposure, and increasing temperature. Studies with synchronized Chinese hamster cells heated at 43 degrees for 1 hr in the presence of 16 mM cysteamine demonstrated that the potentiation of heat killing occurred in all phases of the cell cycle. Similarly, enhancement of hyperthermia-induced cell killing was seen for asynchronous cells exposed to 2-amino-ethylisothiourium bromides and cysteine, but the magnitude of the effect differed for the various sulfhydryl compounds.