Heat shock proteins (HSPs) are though to represent a ubiquitous cellular response to heat or stress. We tested whether HSPs can be induced in hairy cells, other human leukemic cells, and normal lymphocytes, and whether there are additive or synergistic effects between heat shock and interferon-alpha 2b (IFN-alpha 2b) on these cells. We analyzed lysates of cells from 22 patients (6 with hairy cell leukemia, 12 with other acute and chronic leukemias and lymphocytes of 4 normals) after exposure to a heat shock and/or IFN-alpha 2b by one-dimensional polyacrylamide gel electrophoresis. In all cells a pattern of HSPs was readily induced with prominent bands identified at approximately 115, 90, and 65 kD. None of these major proteins appeared to represent the previously described IFN-alpha 2b induced band at 80 kD. IFN-alpha 2b by itself was not found to induce HSPs. We conclude that a pattern of HSPs can readily be induced in a variety of normal and leukemic human blood cells. IFN-alpha 2b is not a HSP inducer in these cells. The previously described IFN-induced p80 is apparently not a HSP.