We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40°C heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0°C air for 30 s when they entered a specific area in an experimental box. Core temperature (T_c) surpassed 40°C in both conditions when 0°C air was not available. Hypertonic saline injection produced a lower baseline T_c than control [36.9 ± 0.2 and 37.9 ± 0.2°C (means ± SE), P < 0.05] and a greater number of 0°C air rewards during the 2-h heat with lower T_c at the end (48 ± 1 and 34 ± 2, 37.6 ± 0.1, and 37.3 ± 0.1°C in the control and hypertonic saline injection trial, respectively, P < 0.05, n = 6). However, T_c was similar (37.7 ± 0.2 and 37.6 ± 0.4°C in the control and hypertonic saline injection trial, n = 5) when 0°C air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline T_c and increasing heat-escape/cold-seeking behavior.