Abstract In the first experiment, mice were placed in a temperature gradient and were permitted to select their ambient temperature ( T a ). After 1 h, the animals were removed from the gradient, injected with mouse urine at doses of 0, 6, 12 or 18 ml/kg (i.p.) and were placed quickly back in the gradient. The 18 ml/kg dose elicited a decrease in the selected T a along with a significant reduction in body temperature measurement at 60 and 120 min post-injection. In a second experiment it was found that urine collected from mice maintained at T a 's of 20, 30 or 35°C overnight had similar effects on the behavioral thermoregulatory response. In the third experiment, mouse urine was dialyzed against saline using dialysis tubing with a molecular cutoff of 1000 Da. The dialyzed urine had no effect on behavioral thermoregulation but did elicit a significant drop in body temperature; however, the decrease in temperature was not as great as that following administration of undialyzed urine. These studies indicate that mouse urine contains toxic substances that evoke a decrease in the set-point (i.e. anapyrexia). Interestingly, the response to urine is similar to that following acute exposure to xenobiotic chemical substances.