Previous in vitro studies of sarcoma and normal cell lines exposed to 41.8 degrees C (x 60 min) demonstrated selective increased expression of members of the heat shock protein (HSP) family 70 on the cell surface of the sarcoma cells only. One implication of these data relates to the clinical application of targeting a stress-inducible, tumor-specific immune response. We therefore elected to measure immune response parameters (i.e., serum antibodies against HSP70i, 60, and 27) in six patients with sarcoma using a Western blot technique. These study patients received one to four successive 41.8 degrees C whole-body hyperthermia (WBH) x 60-min treatments (given every 3 weeks). We also tested the serum of 10 untreated healthy control subjects for the same parameters. In all patients, baseline HSP antibody levels were detectable; in no case did WBH result in an increase in HSP antibodies. The serum of one patient with sarcoma demonstrated a strong nonfluctuating reaction against HSP27 before and after WBH that had no obvious correlation; this was not observed in the sera of the control subjects. This study suggests that WBH does not induce a B-cell response to HSP family 70 antigens; these data, however, do not exclude the possibility of NK cell activation due to HSP antigen presentation.