This study was designed to examine the effects of in vivo hyperthermia on the circulating concentrations of a number of glucoregulatory hormones potentially involved in immunomodulation. Eight healthy male volunteers were immersed for 2 h in a hot water bath (water temperature 39.5 degrees C) (WI) during which period their rectal temperature rose to 39.5 degrees C. In a control study the subjects were immersed in thermoneutral water (water temperature 34.5 degrees C). Blood samples were collected before, at body temperature 38 degrees C (42.5 (30-52), median and range), minutes of hot WI, 39 degrees C (72.5 (58-97) minutes of hot WI), and 39.5 degrees C (at the end of 2 h of hot WI), as well as 1 and 2 h after cessation of 2 h of hot WI. In the control experiment blood samples were collected at identical time points. The growth hormone concentrations were elevated already at 38 degrees C to 24.2 (3.9-55.0) mU/l and peaked at 39 degrees C to 48.4 (20.8-81.5) mU/l compared to 0.3 (0.3-9.0) mU/l at baseline; at 39.5 degrees C the concentration declined to 31.6 (13.0-48.0) mU/l and further to 7.4 (0.8-17.3) mU/l 1 h after ending hot WI. The beta-endorphin levels were augmented at 39 degrees C and 39.5 degrees, to 8.0 (3.4-27.8) pmol/l and 8.1 (3.1-44.6) pmol/l, respectively, from 2.2 (0.7-5.6) pmol/l baseline. Glucagon levels raised from 23.0 (12.0-32.0) pmol/l to 32.0 (24.0-52.0) pmol/l at 39 degrees C, and to 38.5 (26.0-57.0) pmol/l at 39.0 degrees C. Insulin levels remained unchanged. Plasma glucose increased from 4.75 (4.2-7.6) mmol/l to 5.20 (4.6-5.6) mmol/l alone after 90 min of WI (temperature 39-39.5 degrees C). It is concluded that in vivo whole body WI hyperthermia increases the circulating levels of several essential glucoregulatory hormones.