We attempted to assess the prophylactic effect of human umbilical cord blood-derived CD34(+) cells in experimental heatstroke. Anesthetized rats, 1 day before heat stress, were divided into 2 major groups and given CD34(-) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained <0.2% CD34(+) cells) or CD34(+) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained >95% CD34(+) cells). They were exposed to ambient temperature of 43 degrees C for 70 min to induce heatstroke. When the CD34(-) cells-treated or untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Pretreatment with CD34(+) cells significantly increased survival time (123-351 min). As compared with normothermic controls, all CD34(-) cells-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, these heatstroke reactions all were significantly suppressed by CD34(+) cells pretreatment. In addition, the levels of interleukin-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34(+) cell administration during heatstroke. Our data indicate that human umbilical cord-derived CD34(+) cells can be used as a prophylactic agent for experimental heatstroke.