The changes in protein synthesis which result when Tetrahymena thermophila cells are shifted from 30(DEGREES)C to 40(DEGREES)C are shown to be regulated at both the mRNA accumulation and mRNA translation levels. The heat shock protein mRNAs are preferentially translated early in a heat shock while non-heat shock protein messages remain in the cell in a non-translated state. Later in heat shock these non-hsp messages return to polysomes at the same time as a small heat-induced RNA becomes associated with polysomal ribosomes. This novel RNA species may play an important role in the return to normal protein synthesis which signals the end of the heat shock response;The acquired ability of cells to survive normally lethal, >42(DEGREES), temperatures is called thermotolerance. This ability to survive these high temperatures is based on being able to synthesize sufficient quantities of hsps at these temperatures where protein synthesis is normally inhibited. We show the presence of hsps in the cell before a shift to the high temperatures is not required to survive. What is required is that prior to the shift to high temperature the translational machinery of the cell must be altered in some as yet not understood way to allow protein synthesis to occur. This alteration in the translational machinery may be brought about by either a prior 40(DEGREES)C treatment or by exposing cells to low doses of antibiotics which are known to interact with ribosomes.