Three murine lymphoma cell lines, CH1, a B-cell lymphoma, and VL3 and RDM4, both T-cell lymphomas, were tested for their ability to induce heat shock protein synthesis and thermotolerance after heat shock. All three lines could develop thermotolerance, but the persistence of tolerance was less than can be measured in nonlymphoid cell lines. Analysis of protein synthesis patterns by one-dimensional gel electrophoresis suggested that only the VL3 cells were capable of the induction of heat shock proteins. After two-dimensional gel analysis, however, the induction of one heat shock protein was evident in RDM4 cells. No induced heat shock proteins could be detected in the CH1 cells. These data provide strong evidence that, while the induction of heat shock proteins may be sufficient for development of thermotolerance, they are not necessary and that another mechanism is available to cells.