The possibility that the exposure of organisms to whole-body hyperthermia may provide protection against subsequent thermal exposures is intriguing and may play an important role in the clinical scheduling of fractionated hyperthermia. We used C3H mice to investigate whether whole-body heating can be used as a conditioning treatment to induce protection of mice against thermal death from a subsequent heat treatment. Our data clearly show that a conditioning whole-body heat dose (41 degrees for

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... 0 min), by itself nonlethal, can give substantial protection to animals against a later heat treatment. The heat-induced protection is transient in nature: it reaches a maximum by 6 to 24 hr following the 41 degrees conditioning dose and decays by approximately 60% by 72 hr. The data presented do not shed any light on the cause of death following whole-body hyperthermia. Our results show clearly that the response of a complex organism to heat can be altered by previous heat exposure.