The cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.