Heat shock protein (hsp) genes, a group of ubiquitous genes, are activated by various metabolic stresses. The suggestion that denaturation of intracellular proteins may be produced by the metabolic stresses and then signal the activation of the hsp genes was examined by co-injection of purified proteins and hsp genes into frog oocytes. Activation of hsp genes was observed if the proteins were denatured prior to injection but not if they were introduced in their native form. Furthermore, the activation of hsp genes by abnormal proteins and by heat shock appears to occur by a common mechanism. A model for the transcriptional regulation of the genes is based on competition for degradation between abnormal intracellular proteins and a labile regulatory factor.