Responses of Reuber H35 hepatoma cells exposed to increasing doses of heat, arsenite ions, or cadmium ions were investigated. Doses which are capable of activating the heat shock transcription factor (HSF) were determined. The activity of this factor in the poststress period was correlated to the recovery of total protein synthesis in this same period. Subsequently, increases of mRNA levels and rates of synthesis of heat shock protein (HSP)60, HSP68, and HSP84 after exposure to the stressors were determined. We generally found that the rate of HSP synthesis correlated well with HSP mRNA levels, supporting the idea that the stress response is regulated mainly at the transcriptional level. A stressor-specific pattern of HSP mRNA induction can be observed. The most striking example is cadmium chloride which does not induce HSP60 nor its mRNA. Interestingly, under these conditions maximal activation of HSF is observed. Therefore, we conclude that more processes than just HSF activations are involved in the induction of heat shock genes.