Application of a mild heat pretreatment, performed by shifting cells from 27 degrees C to 37 degrees C led to the protection of yeast cells from death due to a subsequent extreme heat shock at 53 degrees C. The presence of cycloheximide inhibited this induction of thermotolerance, indicating the involvement of de novo protein. The phosphatase inhibitor sodium molybdate induced thermotolerance to the non-pretreated yeast cells. This induction of thermotolerance did not seem to depend upon de novo protein synthesis. Thus, acquisition of thermotolerance in yeast may involve a number of cellular mechanisms depending on the conditions the organism encounters at any particular time.